StudyFinder
Search Results
395 Study Matches
Natural History Study for DNA Repair Disorders
A single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD).
Peter Kang
All
6 Months to old
STUDY00015911
STUDY00015911
Inclusion Criteria:
Diagnosis of Cockayne syndrome (CS), xeroderma pigmentosum (XP), or trichothiodystrophy (TTD), based on genetic testing and/or key clinical characteristics l characteristics
Has one or more of the following neurodevelopmental or neurological complications
Gross motor delay (non-ambulatory or started walking after age 18 months)
Language delay (non-verbal or started talking after 18 months)
Altered muscle tone (hypertonia, dystonia, hypotonia)
Gait difficulties, including stiff gait, short stride, frequent falls, use of orthotics, use of walker
Tremors
Microcephaly
Is a family member of an individual with the above condition
No restrictions regarding current ambulatory status
Minimum age for enrollment eligibility will be 6 months due to fragility of neonates with severe forms of DNA repair disorders and limitations of motor assessment scales in infants younger than 6 months. There will be no maximum age for enrollment eligibility.
No restrictions regarding gender, race, or ethnicity.
Voluntary written consent from the participant if adult capable of consenting or parent/guardian if minor or not capable of consenting
Written consent of Legally Authorized Representative if enrolling adult lacks capacity to consent
Exclusion Criteria:
Any prior history of systemic gene or cell-based therapy
Current participation in an interventional clinical trial Interval History, Physical Examination, ECAB Assessment, Gait Assessment, Specimen Sample Collection, Interval History, Physical Examination, ECAB Assessment, Gait Assessment, Specimen Sample Collection
DNA Repair Disorder, Cockayne Syndrome, Xeroderma Pigmentosum, Trichothiodystrophy
A Phase 1, First in Human, Dose-Escalation Study of TORL-1-23 in Participants with Advanced Cancer (TRIO049)
This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-1-23 in patients with advanced cancer.
Boris Winterhoff
All
18 Years to old
Phase 1
STUDY00014893
STUDY00014893
Inclusion Criteria:
Advanced solid tumor
Measurable disease, per RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Adequate organ function
Exclusion Criteria:
Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements
Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-1-23
Progressive or symptomatic brain metastases
Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection
History of significant cardiac disease
History of myelodysplastic syndrome (MDS) or AML
History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded
If female, is pregnant or breastfeeding TORL-1-23, TORL-1-23
Advanced Solid Tumor, Ovarian Cancer, Endometrial Cancer, NSCLC
Clinics and Surgery Center (CSC)
PEPN22P1: Pharmacokinetic Study of VinCRIStine in Infants Dosed According to BSA-Banded Infant Dosing Tables and Older Children Dosed by Traditional BSA Methods
This early phase I trial compares a new method for dosing vincristine in infants and young children to the standard dosing method based on body size in older children. Chemotherapy drugs, such as vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The same dose of a drug cannot be given to all children because they vary a lot in size from infancy to adolescence. The dose of most anticancer drugs is based on a measure of body size called the body surface area (BSA). BSA is calculated from a patient's weight and height. However, infants and young children have more severe side effects if the BSA is used to calculate their dose, so adjustments have to be made to safely give anticancer drugs to the youngest patients. A new method for dosing anticancer drugs in infants and young children has been developed that uses body size to determine the dose. Collecting blood samples over time may help researchers understand how the new vincristine dosing method affects drug levels in the blood over time in infants and young children compared to older children.
Emily Greengard
All
to 12 Years old
STUDY00017658
STUDY00017658
Inclusion Criteria:
Patients must be =< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:
0 to 6 months
6 months and 1 day to 12 months
12 months and 1 day to 36 months
36 months and 1 day to 12 years
Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine at the 1.5 mg/m^2 dose level
Any disease status
Patients must have a Lansky performance status of 50 or higher
Patients must be receiving a treatment regimen that includes 1.5 mg/m^2 vinCRIStine (maximum dose 2 mg)
Patients with a BSA < 0.6 m^2 must be dosed according to the Children's Oncology Group (COG) BSA-banded infant dosing table for the 1.5mg/m2 dose level for vinCRIStine
Note: Patients can be studied after any dose of vinCRIStine
Patients who are NOT enrolled on a COG clinical trial and who have a BSA < 0.6 m^2 and who are being dosed according to another infant dosing method (e.g., the 30-Rule) can receive a dose of vincristine from the infant dosing table for the pharmacokinetic study. These patients will NOT be part of the Dose Modification Assessment
Patients with a seizure disorder may be enrolled if on allowable anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
Nervous system toxicities (Common Terminology Criteria for Adverse Events [CTCAE]) version (v)5 resulting from prior therapy must be grade =< 2
Central venous access device in place (e.g., percutaneous indwelling central catheter [PICC], port, Broviac) that can be used for pharmacokinetic (PK) sampling
VinCRIStine may be given as an outpatient, as long as all sample time points can be collected, which will require return for hour 24 sampling
Exclusion Criteria:
Azoles antifungals and macrolide antibiotics: Patients who are currently receiving an azole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin, or telithromycin) are not eligible
CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances that are considered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible. Moderate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 days prior to enrollment to the end of the study. Note: dexamethasone for central nervous system (CNS) tumors or metastases, on a stable dose, is allowed
Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
Patients with Charcot-Marie-Tooth disease
A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
Patients receiving a modified dose (< 1.5 mg/m^2) of vinCRIStine due to prior toxicity
Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the study Biospecimen Collection, Vincristine, Biospecimen Collection, Vincristine
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
A Phase I Study of HCW9218, a Bifunctional TGF-B; Antagonist/IL-15 Protein Complex, in Select Advanced Solid Tumors After Failing at Least Two Prior Therapies
This is a single center, Phase I dose finding study of HCW9218 for the treatment of select advanced solid tumor cancers, including, but not limited to breast, ovarian, prostate and colorectal. HCW9218 potently activates natural killer (NK) cells and CD8+ T cells in vitro and in vivo to promote their proliferative and metabolic activities and enhance their cytotoxicity against tumor targets. The fusion complex also exhibits TGF-β neutralizing activity in vitro and sequesters plasma TGF-β in vivo. It is hypothesized that HCW9218 may serve as a novel therapeutic to simultaneously provide immunostimulation and lessen immunosuppression associated with solid tumors. The primary objective of this study is to determine the maximum tolerated dose (MTD) of HCW9218 as monotherapy in advanced solid tumor cancers except pancreatic cancer and primary brain tumors.
Melissa Geller, MD
All
18 Years to old
Phase 1
STUDY00015102
STUDY00015102
Inclusion Criteria:
Histologically or cytologically confirmed advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers), has failed at least 2 prior lines of therapy given either in the recurrent or metastatic setting and must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Measurable disease per RECIST v 1.1.
Acute effects of any prior therapy must have resolved to baseline or Grade ≤1 NCI CTCAE v5 except for AEs not constituting a safety risk by enrolling Investigator judgment.
Age 18 years or older at the time of consent.
ECOG Performance Status 0 or 1.
Evidence of adequate organ function within 14 days prior to enrollment as defined in Section 4.1.6.
Adequate pulmonary function with PFTs >50% FEV1 if symptomatic or known impairment.
Sexually active persons of child-bearing potential or with partners of childbearing potential must agree to use a highly effective form of contraception (refer to Section 4.1.10 for acceptable methods) for at least 28 days after the last dose of HCW9218.
Provides voluntary written consent prior to the performance of any research related activity.
Exclusion Criteria:
Pregnant or breastfeeding.
History of clinically significant vascular disease, including any of the following within 6 months prior to start of study treatment: MI or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease.
Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval greater or equal to 470 milliseconds by Fridericia's correction).
Known or suspected untreated CNS metastases.
Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start.
Other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease-free for 3 years after surgical treatment.
Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
Prior therapy with TGF-β antagonist, IL-15 or analogs.
Concurrent use of St. John's wort and and/or other herbal CYP modulators within 7 days of Day 1. Must agree to not use during study treatment through the end of treatment visit to be eligible.
Known autoimmune disease requiring active treatment. Persons with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
Prior organ allograft or allogeneic transplantation.
Known HIV-positive or AIDS.
Psychiatric illness/social situations that would limit compliance with study requirements.
Other illness or a medical issue that in the opinion of the Investigator would exclude the subject from participating in this study HCW9218, HCW9218
Solid Tumor
Clinics and Surgery Center (CSC), Phase I Clinic
A randomized, participant and investigator blinded, sponsor open-label, placebo-controlled, single dose study to investigate the safety and tolerability of XXB750 in heart failure participants with reduced ejection fraction (HFrEF)
This is a multi-center, randomized, sponsor open-label, participant and investigator blinded, placebo-controlled, single dose study to investigate the safety and tolerability of a single subcutaneous dose of XXB750 in HFrEF.
Les Forgosh
Male or Female
18 Years and over
Phase I
STUDY00015604
STUDY00015604
Inclusion Criteria:
-Men or women age 18 to 75 years
-NYHA functional class II-III
-LVEF greater than or equal to 45% documented at screening
-Systolic blood pressure 110-180 mmHg and heart rate less than or equal to 90 beats per minute
-On stable therapies of ACE inhibitor/ARB and beta-blocker for 4 weeks prior to screening
Exclusion Criteria:
-Acute heart failure, acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
-Hemodynamically significant mitral and/or aortic calve disease, except mitral regurgitation secondary to LV dilatation at screening
-Implantation of a CRT device within 3 months prior to screening or intent to implant a CRT during the study period
-History of severe pulmonary disease (e.g. COPD) requiring chronic supplemental oxygen therapy or pulmonary hypertension requiring pharmacology treatment at Screening
-eGFR less than 45 mL/min/1.73m^2 at screening
-Treatment with Sacubitril/Valsartan currently or within 2 weeks from screening
-BMI greater than 35 kg/m^2 XXB750, Placebo, XXB750, Placebo
Heart & Vascular
HFrEF, Heart Failure
STUDY OF PHIL?? EMBOLIC SYSTEM IN THE TREATMENT OF INTRACRANIAL DURAL ARTERIOVENOUS FISTULAS (PHIL dAVF)
Arteriovenous fistulas are a type of arteriovenous malformation whereby blood is shunted directly from the arterial system to the venous system, bypassing the capillary bed. Dural arteriovenous fistulas (dAVFs) are a rare type of acquired intracranial vascular malformation consisting of a pathologic shunt located within the dura mater of the brain. 1 These lesions have been categorized by Awad et al 2, Borden et al 3, and Cognard et al 4 according to their locations and patterns of venous drainage. Dural arteriovenous fistulas (dAVFs) can be observed anywhere on the dural layer meninges of the cranium and spine. This condition accounts for 10-15% of all intracranial arteriovenous malformations diagnosed. 5 These fistulas can be congenital or acquired diseases. When observed as acquired diseases, they are most often encountered in males between the age of 50 and 60 years old. DAVFs present with a wide spectrum of symptoms or none at all, and come with varying range of risk of clinical sequalae. A thorough evaluation of the anatomy and venous drainage is crucial to determining the best treatment strategy. Acute presentation with intracranial hemorrhage occurs in up to 65% of patients, and patients with a previous intracranial hemorrhage may have up to a 35% risk of another neurologic event within 2 weeks. 6 Endovascular embolization has become the primary treatment approach for DAVFs. The goal of endovascular therapy is to achieve complete obliteration of the fistulous point between the feeding arteries and the draining veins. This can be safely accomplished by occluding the draining veins, which often results in complete closure of the lesion, unlike in cerebral arteriovenous malformations. The PHIL® device is a non-adhesive liquid embolic agent comprised of a Triiodophenol-(lactide-co-glycolide) acrylate and hydroxyethyl methacrylate (HEMA) co-polymer dissolved in DMSO (dimethyl sulfoxide). An iodine component is chemically bonded to the co-polymer to provide a radiopacifier element during fluoroscopic visualization. The PHIL® Liquid Embolic System consists of a sterile, pre-filled, 1.0 mL syringe of PHIL® liquid embolic, a sterile, prefilled 1.0 mL syringe of DMSO, and microcatheter hub adaptors. Intracranial dAVFs may produce a wide variety of symptoms. Individual risk is evaluated by a precise analysis of the venous drainage. The decision to treat is based on this analysis. Treatment strategy is decided by a multidisciplinary neurovascular team and must consider the individual risk of each dAVF. Embolization is, in most cases, proposed as the first treatment option and often succeeds to obtain a complete and definitive cure of the dAVF. Surgery may be required in some locations or in the case of embolization failure. Radiosurgery is rarely indicated because it is not always efficient and because of the time required for shunt obliteration and the risk of bleeding in this period. Liquid embolics have distinct characteristics that make them a principle treatment option in the obliteration of dAVFs. They can flow through complex vascular structures so that the surgeon does not need to target the catheter to every single vessel. 10 There is little choice available in the US market for the liquid embolic treatment of dAVF. Currently, nBCA (TRUFILL n-Butyl Cyanoacrylate, Cordis) and Onyx (Medtronic) are the only liquid embolic agents available. Both are approved by FDA for presurgical embolization of cerebral arteriovenous malformations. However, they have been used off-label for dAVFs. This use demonstrates the unmet medical need for the patients suffering with dAVFs. The aim of this study is to evaluate the use of PHIL in the management of intracranial dural AVFs.
Ramu Tummala
All
22 Years to 80 Years old
Phase I/II
STUDY00003548
STUDY00003548
Inclusion Criteria:
Age 22 - 80 years.
Subject is willing and capable of complying with all study protocol requirements, including specified follow-up period.
Subject or authorized legal representative must provide written informed consent prior to initiation of any study procedures.
Subject has an intracranial dAVF
Exclusion Criteria:
Subject having multiple dAVFs to be treated.
Subject with a history of life threatening allergy to contrast media (unless treatment for allergy is tolerated).
Subject has known allergies to dimethylsulfoxide, iodine.
Subject is currently participating in another clinical study
Female subject is currently pregnant.
Subject has co-morbid conditions that may limit survival to less than 24 months. PHIL® Liquid Embolic System, PHIL® Liquid Embolic System
Arteriovenous Dural Fistula
Arteriovenous, Dural, Fistula, Intracranial, Liquid Embolic
A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, a AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects with Fabry Disease
Chester Whitley, MD, PhD
All
18 Years to old
Phase 1/Phase 2
STUDY00007094
STUDY00007094
Inclusion Criteria:
≥ 18 years of age
Documented diagnosis of Fabry disease
One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma
Subject must be fully vaccinated (as per the Centers for Disease Control and Prevention (CDC) definition in the US and as per local guidelines in other countries) for COVID-19 at least one month prior to dosing
Additional Inclusion Criteria:
Renal Cohort:
Screening eGFR value between 40-90 mL/min/1.73 m²
Linear negative eGFR slope (estimated from at least 3 serum creatinine values within 18 months, including the value obtained during screening visit) of ≥ 2 mL/min/1.73m²/year
Cardiac Cohort:
• Left ventricular hypertrophy (LVH) in 2D echocardiography or CMR defined as an end diastolic septum and posterior wall thickness ≥12 mm with no other explanation for LVH, OR presentation with cardiac changes indicative of disease progression such as decreased global longitudinal strain on 2D strain echocardiography or low native T1 mapping on CMR
Exclusion Criteria:
Neutralizing antibodies to AAV6
eGFR < 40 ml/min/1.73m2
New York Heart Association Class III or higher
Active infection with hepatitis A, B or C, HIV or TB
History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; except for Gilbert's syndrome
Elevated circulating serum AFP
Recent or recurrent hypersensitivity response to ERT within within 6 months prior to consent
Current or history of systemic (IV or oral) immunomodulatory agents, or biologics or steroid use in the past 6 months prior to consent (topical treatment and inhaled allowed).
Contraindication to use of corticosteroids
History of malignancy except for non-melanoma skin cancer and localized prostate cancer treated with curative intent
Recent history of alcohol or substance abuse
Participation in investigational interventional drug or medical device study throughout the duration of this study and within previous 3 months prior to consent
Prior treatment with a gene therapy product
Known hypersensitivity to components of ST-920 formulation
Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study including but not limited to risk of COVID-19 infection
Additional exclusion criteria for:
Renal cohort:
History of renal dialysis or transplantation
History of acute kidney insufficiency in the 6 months prior to screening
Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening
Urine protein to creatinine ratio (UPCR) > 0.5 g/g who are not being treated with an ACE inhibitor or ARB
Cardiac cohort:
Significant cardiac fibrosis defined by late gadolinium enhancement on CMR
Any contraindications to CMR as per local hospital/institution guidelines
Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening
NYHA Class IV ST-920, ST-920
Fabry Disease
Sangamo, Rare, Lysosomal Storage Disease, Gene Therapy
A Phase 1/2 Study of the Oral RET Inhibitor LOXO-292 in Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors; Protocol Number: LOXO-RET-18036 (J2G-OX-JZJJ) (LIBRETTO-121)
This is an open-label, multi-center, Phase 1/2 study of oral LOXO-292 in pediatric patients with an activating RET alteration and an advanced solid or primary CNS tumor.
Emily Greengard
All
6 Months to 21 Years old
Phase 1/Phase 2
STUDY00008874
STUDY00008874
Inclusion Criteria:
Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
Evidence of an activating RET gene alteration in the tumor and/or blood
Measurable or non-measurable disease
Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
Adequate hematologic, hepatic and renal function.
Ability to receive study drug therapy orally or via gastric access
Willingness of men and women of reproductive potential to observe conventional and effective birth control
Exclusion Criteria:
Major surgery within two weeks prior to planned start of LOXO-292
Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
Clinically significant active malabsorption syndrome
Pregnancy or lactation
Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
Uncontrolled symptomatic hypercalcemia or hypocalcemia
Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s]) LOXO-292, LOXO-292
Medullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma, Papillary Thyroid Cancer, Soft Tissue Sarcoma
Infantile Myofibromatosis, Infantile Fibrosarcoma, Loxo, LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Adenoma, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Colonic Neoplasms, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, Soft tissue sarcoma
A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients with Advanced Solid Tumors with KRAS G12C Mutation
This is an early study of a new drug, MRTX849, to treat certain solid tumors that have not responded to usual treatment. The tumor must have a KRAS G12C mutation. We are testing the drug to see if it is effective in treating the cancer and what side effects occur.
Amit Kulkarni
All
18 Years to old
Phase 1/Phase 2
STUDY00009695
STUDY00009695
Inclusion Criteria:
Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
Unresectable or metastatic disease
Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts
Adequate organ function
Exclusion Criteria:
History of intestinal disease or major gastric surgery or inability to swallow oral medications
Other active cancer MRTX849, Pembrolizumab, Cetuximab, Afatinib, MRTX849, Pembrolizumab, Cetuximab, Afatinib
Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
Clinics and Surgery Center (CSC), Phase I Clinic
A Phase 1/2, Multi-Center, Dose-Escalating Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Quizartinib Administered in Combination with Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to < 18 Years (and Young Adults Aged up to 21 Years) with FLT3-ITD Mutations (Protocol Number: AC220-A-U202/ADVL1822)
This is an open-label, multi-center, single arm, Phase 1/2 study to evaluate the safety, PK, PD, and efficacy of quizartinib administered in combination with fludarabine and cytarabine (FLA) (Re-Induction Cycles 1 and 2) chemotherapy for re-induction, with optional consolidation chemotherapy, and as a single agent continuation therapy (after optional, but strongly encouraged, HSCT per standard of care), in pediatric relapsed/refractory AML subjects aged ≥1 month old to <18 years old (and young adults up to 21 years old) with FLT3-ITD mutations.
Emily Greengard
All
1 Month to 21 Years old
Phase 1/Phase 2
STUDY00005937
STUDY00005937
Inclusion Criteria:
Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
Is in first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
Has protocol-defined adequate performance status score
Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
Has protocol-defined adequate renal, hepatic and cardiac functions
If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of study drug or cytarabine, whichever is later
If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
Meets protocol-specified guidelines before inclusion in the continuation therapy phase
Exclusion Criteria:
Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, or with myeloid proliferations related to Down syndrome
Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
Has known history of human immunodeficiency virus (HIV)
Has history of hypersensitivity to any of the study medications or their excipients
Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
Is otherwise considered inappropriate for the study by the Investigator Quizartinib, Intrathecal (IT) triple chemotherapy prophylaxis, Fludarabine, Cytarabine, Etoposide, Quizartinib, Intrathecal (IT) triple chemotherapy prophylaxis, Fludarabine, Cytarabine, Etoposide
Acute Myeloid Leukemia
Acute myeloid leukemia recurrent, Relapsed or refractory, FMS-like tyrosine kinase 3 positive, Cancer of the blood, AML, FLT3-ITD mutation
A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of the Safety and Pharmacodynamic Activity of Gene Therapy for Congenital Adrenal Hyperplasia through Administration of an Adeno-associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2 Gene
This is a Phase 1/2, first-in-human, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of BBP-631 administered to up to 25 adult participants diagnosed with classic congenital adrenal hyperplasia (CAH) (simple virilizing or salt-wasting, Group 1) or with classic salt-wasting CAH (Group 2) due to 21-hydroxylase deficiency (21-OHD) and who are monitored for 24 weeks posttreatment.
Kyriakie Sarafoglou
All
18 Years to old
Phase 1/Phase 2
STUDY00012144
STUDY00012144
Key Inclusion Criteria
Adult male and non-pregnant females with classic CAH (simple virilizing or salt-wasting) due to 21-OHD
Screening/baseline 17-OHP levels > 5-10 × ULN and < 40 × ULN (upper limit of normal)
Stable oral hydrocortisone (HC) regimen as the only glucocorticoid (GC) maintenance therapy
Naïve to prior gene therapy or AAV-mediated therapy
Key Exclusion Criteria
Positive for anti-AAV5 (Adeno-Associated Virus Type 5) antibodies
History of adrenalectomy and/or significant liver disease
AAV BBP-631, AAV BBP-631
Congenital Adrenal Hyperplasia
CAH, Gene therapy, AAV, AAV5
MT2020-27: Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to Tisagenlecleucel (Kymriah) Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
This purpose of this study is to identify a safe dose level for the study drug, E7777, when given with standard tisagenlecleucel therapy (also known by its brand name, Kymriah, is an immunotherapy that is made from the participants own blood cells) in participants with Diffuse Large B-Cell Lymphoma (DLBCL). Up to three dose levels of E7777 will be tested.
Veronika Bachanova, MD
All
18 Years to old
Phase 1/Phase 2
STUDY00011895
STUDY00011895
Inclusion Criteria:
Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including:
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
high grade B-cell lymphoma
DLBCL arising from follicular lymphoma
Considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
refractory to last line of therapy
myc over expression >40% in any prior biopsy
≥2 sites of extranodal disease
Received two or more lines of systemic therapy
Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting.
Age 18 years or older at the time of signing consent.
ECOG performance status of 0, 1, or 2
Adequate bone marrow reserve defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
Adequate organ function at enrollment and within 14 days of planned E7777 treatment including:
renal function: eGFR ≥ 50 mL/min/1.73 m^2
liver function: ALT ≤ 3 times the upper limit of normal (ULN) for age, AST ≤ 3 times the ULN, total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
albumin ≥ 3.0 g/dl
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 > 91% on room air. Pulmonary function tests within 28 days of enrollment: >50% corrected DLCO and FEV1
Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
Life expectancy ≥12 weeks in the opinion of the enrolling investigator as documented in the medical record
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
Written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
Prior allogeneic transplant
Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion E7777, E7777
DLBCL, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, DLBCL Arising From Follicular Lymphoma
Clinics and Surgery Center (CSC)
An Open-label, Phase 1/2 Study to Evaluate the Safety and Efficacy of Single-dose PR001A in Infants with Type 2 Gaucher Disease
This is a study to assess the safety and efficacy of PR001A, an Aden-associated (AAV9) viral vector to treat neuronopathic Gaucher disease type 2 (GD2) in infants. PRA001A will be administered via suboccipital injection to the cisterna magna during a single neurosurgical session. GD2 is a fatal disease of early infancy that does not have any therapeutic options beyond palliative care. This study will enroll infants 0-24 months of age.
Chester Whitley, MD, PhD
All
0 Months to 24 Months old
Phase 1/Phase 2
STUDY00008823
STUDY00008823
Inclusion Criteria:
Bi-allelic GBA1 mutations consistent with a diagnosis of GD2 confirmed by the central laboratory.
Clinical diagnosis of GD2
Parent/legal guardian has the ability to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
Patient has a reliable informant (i.e., parent/legal guardian) willing and able to participate in the study as a source of information on the patient's health status and cognitive and functional abilities (including providing input into the rating scales).
Exclusion Criteria:
Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound study objectives.
Achieved independent gait.
Severe peripheral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
Concomitant disease, condition, or treatment which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
Use of any GD treatment-related substrate reduction therapy.
Use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
Any type of prior gene or cell therapy.
Live vaccine Immunizations within 4 weeks, or non-live vaccines within 2 weeks prior to the start of required immunosuppressive regimen.
Use of blood thinners. Antiplatelet therapies are acceptable if the patient is medically able to temporarily stop them from 7 days prior to dosing and through at least 48 hours after the intracisternal injection and lumbar puncture.
Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical or inhaled preparations for dermatological conditions or asthma are allowed).
Participation in another investigational drug or device study within the past 3 months.
Brain MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography) showing clinically significant abnormality deemed a contraindication to intracisternal injection.
Clinically significant laboratory test result abnormalities assessed at screening.
Contraindications or intolerance to radiographic visualization methods (e.g. MRI, MRA, CT), and intolerance to contrast agents used for MRI or CT scans.
Contraindications to general anesthesia or sedation.
Other protocol-defined inclusion/exclusion criteria may apply. LY3884961, Methylprednisolone, Sirolimus, Prednisone, LY3884961, Methylprednisolone, Sirolimus, Prednisone
Gaucher Disease, Type 2
Gaucher Disease, GD, Gaucher, Type 2 Gaucher, Neuronopathic Gaucher, nGD, AAV9, GBA, Gene Therapy, Glucocerebrosidase, GBA1 mutation, Infants
EPI-MINN: Targeting Cognition and Motivation in Coordinated Specialty Care for Early Psychosis
The purpose of this study is to perform a practice-based research project designed to assess whether cognition and motivated behavior in early psychosis can be addressed as key treatment goals within real-world settings by using a 12-week mobile intervention program. The aim of this study is to investigate a well-defined 12-week mobile intervention program specifically designed to target cognitive functioning and motivated behavior for individuals with early psychosis. We will test for differences in the clinical trajectories over 18 months in those who receive the intervention vs. those who do not.
Sophia Vinogradov
All
15 Years to 40 Years old
N/A
STUDY00011512
STUDY00011512
Inclusion Criteria:
Enrolled in EPI-MINN: Measurement Based Care protocol, STUDY00009334
Good general health (i.e. not acutely ill or experiencing a severe/chronic illness that would impede their ability to complete study activities. This determination shall be, if necessary, made at the discretion of the PIs)
Estimated IQ at or above 70, as estimated by the Penn CNP Matrix Reasoning Test
Achieved clinical stability, defined as outpatient status for at least one month prior to study participation and clinically stable doses of psychiatric medication (by PI discretion) for at least one month prior to study participation (including no medication)
Has access to a smartphone or other mobile device to use the PRIME app
Exclusion Criteria:
Under legal commitment to treatment or is under medical guardianship, and there is no provision in the guardianship order or a court order to allow the guardian to consent to participation in research
Participated in significant cognitive training programs within the last three years
Diagnosed with a neurological disorder (Autism Spectrum Disorder is allowed)
Clinically significant substance abuse that is impeding the participant's abulity to participate fully during recruitment, enrollment, assessment, or training, (is unable to remain sober for assessments and training)
Risk of suicidal behavior, as indicated by the clinicall obtained C-SSRS or clinician judgement. Risk of suicidal behavior is defined as:
Active suicidal ideation at screening or baseline, or
Previous intent to act on suicidal ideation with a specific plan, preparatory acts, or an actual suicide attempt within the last 3 months Cognitive and Social Cognitive Training, Personalized Real-Time Motivational Enhancement (PRIME) App, Cognitive and Social Cognitive Training, Personalized Real-Time Motivational Enhancement (PRIME) App
Psychosis
Cognitive Training, Motivation Enhancement, First Episode Psychosis, Schizophrenia Spectrum Disorders
Clinical Study of Neuspera's Implantable Sacral Nerve Stimulation (SNS) System in Patients with Symptoms of Urinary Urgency Incontinence (UUI)
Prospective, multi-center, single-arm, seamless phase-pivotal study conducted in participants diagnosed with UUI who have failed or could not tolerate more conservative treatment. The trial will be conducted in two phases. Objective of Phase I: To assess the utilization of the system during the Sacral Nerve Stimulation (SNS) trial period and to help inform the length of hours of daily stimulation to be used in Phase II of the trial. Objective of Phase II: To assess the safety and efficacy of the Neuspera SNS System at 6-months for the primary efficacy endpoint and at 12 months for secondary safety and efficacy endpoints.
Nissrine Nakib
All
22 Years to old
Phase I/II
STUDY00016099
STUDY00016099
Inclusion Criteria:
Has a Body Mass Index (BMI) between 18 and 40.
Has a diagnosis of UUI for greater than or equal to 6 months prior to the screening baseline visit date.
Has failed or was not a candidate for more conservative treatment (e.g. pelvic floor training, biofeedback, behavioral modification).
Has failed or could not tolerate (stopped taking medication due to lack of efficacy or intolerable side effects) at least one (1) antimuscarinic or β3 adrenoceptor agonist medication.
Has a diagnosis of UUI with at least 4 UUI episodes on a 72-hour diary, and minimum of one (1) UUI episode per 24-hour period.
Exclusion Criteria:
Has a hemoglobin A1c of greater than 8 percent, or has diabetes mellitus with glucosuria.
Has diabetic neuropathy.
Has interstitial cystitis or bladder pain syndrome as defined by either American Urological Association (AUA) or European Association of Urology (EAU) guidelines, chronic pelvic pain or recurrent symptomatic urinary tract infections.
Has neurogenic bladder dysfunction such as traumatic or atraumatic myelopathy, multiple sclerosis, Parkinsonism, or history of cerebrovascular accident.
Has documented urinary retention within 6 months prior to the screening baseline visit date.
Has clinically significant bladder outlet obstruction.
Is a subject with a mechanical obstruction such as benign prostatic hypertrophy, urethral stricture or cancer.
Has primary stress incontinence or mixed incontinence where the stress component predominates or has been treated surgically for stress urinary incontinence within 6 months prior to the screening baseline visit date.
Has received tibial nerve stimulation (TNS) in the past 3 months for the treatment of overactive bladder or unwilling to stay off TNS therapy for 12-month period following implant. Neuspera Implantable Sacral Nerve Stimulation System, Neuspera Implantable Sacral Nerve Stimulation System
Urinary Urgency Incontinence
Clinics and Surgery Center (CSC)
MT2021-25: Phase I/II Multicenter study evaluating the Safety and Efficacy of Alllogeneic GDA-201 Natural Killer cells in patients with relapsed/refractory B-Cell Non-Hodgkin Lymphoma
This study is designed to assess the safety of GDA-201 + rituximab, as well as the maximum tolerated dose in patients with B cell lymphomas in phase I; in phase II, it will assess safety and efficacy of GDA-201 in cohorts of patients with follicular lymphoma, high grade B cell lymphoma (including diffuse large B-cell), high grade B cell lymphoma not otherwise specified, and primary mediastinal B cell lymphoma.
Veronika Bachanova, MD
All
18 Years to old
Phase 1/Phase 2
STUDY00015044
STUDY00015044
Inclusion Criteria:
Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows:
Received at least 2 prior lines of therapy
Transplant ineligible patients allowed assuming they meet criterion a.
Patients who received prior chimeric antigen receptor modified T-cells (CAR-T) cell therapy or are considered ineligible for CAR-T therapy per the investigator's discretion
FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL
Patients must be at least 18 years of age
Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.
Exclusion Criteria:
CNS lymphoma
Time between previous treatment and first dose of study treatment (rituximab):
Allogeneic HSCT < 6 months prior to study treatment
Autologous HSCT < 3 months prior to study treatment
CAR-T < 2 months prior to study treatment GDA-201, GDA-201
Non-Hodgkin Lymphoma
Clinics and Surgery Center (CSC)
MT2021-01: PTCy + Sirolimus/VIC-1911 as GVHD prophylaxis in myeloablative PBSC transplantation
The primary objective of this study is to determine the optimal dose of VIC-1911 when given in combination with standard immunosuppressive therapy in adult patients undergoing myeloablative stem cell transplantation.
Shernan Holtan
All
18 Years to old
Phase 1/Phase 2
STUDY00015049
STUDY00015049
Inclusion Criteria:
Diagnosis of
acute leukemia in complete remission, or
myelodysplasia with <5% blasts, or
myeloproliferative neoplasm/myelofibrosis with <5% marrow or circulating blasts
chemosensitive Hodgkin or non-Hodgkin lymphoma
Age 18 years or older
Performance status of ≥ 80% Karnofsky
Adequate organ function within 28 days of study registration defined as:
left ventricular ejection fraction ≥ 45%
pulmonary function with FEV1, FVC, and DLCO ≥ 50% predicted
AST and ALT < 2 times upper limit of normal
Total bilirubin <1.5 times the upper limit of normal. If the patient is suspected of having Gilbert syndrome, they require prior approval of the medical monitor
creatinine clearance ≥ 50cc/min
no active/uncontrolled infection
negative HIV, HBV and HCV
ferritin < 2000 ng/ml
Patients able to tolerate oral medication
Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment through 60 days after the last treatment of VIC-1911 or sirolimus
Able to provide written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
HCT-CI > 4 or unable to receive myeloablative TBI
Use of planned post-transplant maintenance therapy to begin prior to day +75. Patients may receive standard of care maintenance therapies starting at day
+75 or later
Patients with a history of hypersensitivity to any of the investigational products
Pregnant or breastfeeding as agents used in this study are Pregnancy Category
o C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, and Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 28 days of study registration.
Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 60 days after the last treatment of VIC-1911 or sirolimus VIC- 1911, VIC- 1911
Acute Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Lymphoma
Clinics and Surgery Center (CSC)
20-0001: A Phase 1b/2, Multi-Centered, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Microbiological Activity of a Single Dose of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized with Pseudomonas aeruginosa
This clinical trial is designed to describe the safety and microbiologic activity of bacteriophages directed at P. aeruginosa in clinically stable CF subjects with P. aeruginosa respiratory colonization. This is a dose-ranging study of IV anti-pseudomonal bacteriophage therapy.
Joanne Billings
All
18 Years to 99 Years old
Phase 1/Phase 2
STUDY00013957
STUDY00013957
Inclusion Criteria:
Subjects must meet all the inclusion criteria to be eligible to participate in the study:
Adult (>/= 18 years) at the time of screening.
Confirmed CF diagnosis based on a compatible clinical syndrome confirmed by either an abnormal sweat chloride testing or two CFTR gene variations.*
*Can be obtained from documentation in medical records; actual test results not necessary.
Likely able to produce at least 2 mL of sputum during a 30-minute sputum collection following a hypertonic saline treatment or other approach to increase sputum production.*
**Determined by investigator or their designee judgement. Approaches for obtaining sputum may include, but are not limited to, inhaled hypertonic saline (e.g. 3%, 7%, or 10%), inhaled hypertonic bicarbonate, inhaled mannitol, or spontaneously expectorated sputum. The same approach should be used for all sputum collections for a given subject.
P. aeruginosa (regardless of Colony Forming Units (CFU)/mL) isolated from a sputum, throat culture, or other respiratory specimen in the past 12 months.
Confirmed P. aeruginosa isolation from a sample of expectorated sputum at the Screening Visit.
Capable of providing informed consent.
Capable and willing to complete all study visits and perform all procedures required by the protocol.
Exclusion Criteria:
Subjects who meet any of the exclusion criteria will not be enrolled in the study:
Body weight < 30 kg.
Forced Expiratory Volume 1 second < 20% of predicted value at screening, using the Hankinson equations.
Elevated LFTs obtained at screening.*
*a. Alanine aminotransferase (ALT) > 5 x the upper limit of normal (ULN) or aspartate transaminase (AST) > 5 x ULN or total bilirubin > 3 x ULN, OR b. Total bilirubin > 1.5 x ULN combined with either ALT > 3 x ULN or AST > 3 x ULN. ULN reflects local laboratory ranges.
Acute clinical illness requiring a new (oral, parenteral), or inhaled antibiotic(s) 45 years old and has gone at least 12 months without a spontaneous menstrual period without other known or suspected cause.
Effective methods of contraception include (a) abstinence, (b) partner vasectomy, (c) intrauterine devices, (d) hormonal implants (such as Implanon), or (e) other hormonal methods (birth control pills, injections, patches, vaginal rings).
Active treatment of any mycobacterial or fungal organisms Placebo, WRAIR_PAM-CF1, Placebo, WRAIR_PAM-CF1
Rare Diseases
Bacteriophage therapy, Cystic Fibrosis, Microbiological Activity, Pseudomonas aeruginosa, Safety
A Phase IB/II Multi-Cohort Study of Targeted Agents with Atezolizumab for Patients with Recurrent or Persistent Endometrial Cancer (EndoMAP)
The purpose of this study is to learn the effects, good or bad, of several possible study treatments for EndoCA that are selected based on genetic markers that can be found in these tumors.
Britt Erickson
Female
18 Years to old
Phase 1/Phase 2
STUDY00013241
STUDY00013241
Key
Inclusion Criteria:
Recurrent or persistent endometrial carcinoma which has progressed or recurred after at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit. Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be counted as a systemic therapeutic regimen.
Measurable disease per RECIST 1.1
Availability of a representative tumor specimen that is suitable for determination of biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report from 1 September 2019 or later, those NGS results can be used to determine biomarker status as long as the tumor tissue used in the report was obtained within 5 years prior to prescreening and appropriate signed consent is obtained from the patient.
Life expectancy > 12 weeks
Recovery from effects of recent radiotherapy, surgery, or chemotherapy
Key Exclusion Criteria:
Endometrial tumors with the following histologies: squamous carcinomas, sarcomas
Other invasive malignancies within the last 5 years, except for non-melanoma skin cancer with no evidence of disease within the past 5 years AND localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed > 5 years ago
Synchronous primary invasive ovarian or cervical cancer
Have an active or history of autoimmune disease or immune deficiency
Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a screening chest computed tomography (CT) scan
Active tuberculosis
Severe infections within 4 weeks
Have received therapeutic oral or IV antibiotic medication within 2 weeks, except prophylactic antibiotic medication
Have significant cardiovascular disease
Are administered treatment with a live attenuated vaccine within 4 weeks, or anticipation of need for such a vaccine during the course of the study
Have prior allogeneic bone marrow transplantation or solid organ transplant
Prior treatment with T-cell costimulating or immune checkpoint blockade therapies including, but not limited to, CD137 agonists, anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapeutic antibodies
History of treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
History of treatment with systemic immunosuppressive medications within 2 weeks except acute, low-dose, systemic immunosuppressant medications, corticosteroids for chronic obstructive pulmonary disease and asthma, or mineralocorticoids and low-dose corticosteroids for participants with orthostatic hypotension or adrenocortical insufficiency
Have a history or clinical evidence of any untreated CNS disease, seizures not controlled with standard medical therapy, or history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months
Note: Additional study cohort specific inclusion and exclusion criteria may apply based on cohort assignment. Atezolizumab - 28 Day Cycle, Bevacizumab, Ipatasertib, Talazoparib, Trastuzumab emtansine, Tiragolumab, Atezolizumab - 21 Day Cycle, Inavolisib, Letrozole, Atezolizumab - 28 Day Cycle, Bevacizumab, Ipatasertib, Talazoparib, Trastuzumab emtansine, Tiragolumab, Atezolizumab - 21 Day Cycle, Inavolisib, Letrozole
Endometrial Cancer
Clinics and Surgery Center (CSC)
PEPN2011 - A Phase 1/2 Study of Tegavivint (IND#156033, NSC#826393) in Children, Adolescents, and Young Adults with Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
This phase I/II trial evaluates the highest safe dose, side effects, and possible benefits of tegavivint in treating children, adolescents, and young adults with recurrent or refractory solid tumors, including lymphomas and desmoid tumors.
Emily Greengard
All
12 Months to 30 Years old
Phase 1/Phase 2
STUDY00014319
STUDY00014319
Inclusion Criteria:
PART A: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
PART B: Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Non-Hodgkin lymphoma patients
A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine [6MP], and/or methotrexate)
>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell Infusions (with or without total-body irradiation [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 42 days.
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.).
External beam radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have received prior exposure to tegavivint
PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):
Age; maximum serum creatinine
Age 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
Age 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
Age 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
Age 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
Age 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
Age >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)
PATIENTS WITH SOLID TUMORS: Albumin >= 2 g/dL (within 7 days prior to enrollment)
Exclusion Criteria:
Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
Patients who have received denosumab within 180 days prior to study enrollment will be excluded
Patients with primary brain tumors are ineligible
Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
Patients with a disorder associated with abnormal bone metabolism will be excluded
Patients with grade >= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
Patients with vitamin D < 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
Patients with pre-existing grade 3 osteoporosis are excluded
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Dual X-ray Absorptiometry, Tegavivint, X-Ray Imaging, Dual X-ray Absorptiometry, Tegavivint, X-Ray Imaging
Colorectal Carcinoma, Endometrial Carcinoma, Melanoma, Neuroblastoma, Ovarian Carcinoma, Pancreatic Ductal Adenocarcinoma, Recurrent Desmoid Fibromatosis, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Hepatocellular Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Refractory Desmoid Fibromatosis, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Hepatocellular Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Solid Pseudopapillary Neoplasm of the Pancreas, Wilms Tumor
A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients with Locally Advanced or Metastatic Solid Tumours
This is an early study of a new drug, called [225Ac]-FPI-1434, to treat solid tumors that have not responded to usual treatment. We are testing different doses of the drug and looking at how well it works for treating the cancer and side effects that occur.
Douglas Yee, MD
All
18 Years and over
Phase 1/Phase 2
STUDY00013618
STUDY00013618
Inclusion Criteria:
Pathologically documented, definitively diagnosed, advanced solid tumour that is refractory to all standard treatment, for which no standard treatment is available, or it is contraindicated, or the patient refuses standard therapy.
Measurable or evaluable disease in accordance with RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
Life expectancy of greater than 3 months as judged by the treating physician.
Available tumour tissue (either archival or fresh biopsy) for IGF-1R immunohistochemistry. Submission of the tissue is not required prior to enrollment.
Adequate heart, kidney, and liver function
Adequate bone marrow reserves
Ability to understand and the willingness to sign a written informed consent document.
Phase 2 Specific
Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, metastatic, or recurrent solid tumour types: endometrial, cervical, ovarian, TNBC, HER 2-negative breast, HNSCC, ACC, or uveal melanoma.
Have measurable disease per RECIST 1.1 Failure to respond to standard systemic therapy, or for whom standard or curative systemic therapy does not exist or is not tolerable.
Imaging Eligibility
Prior to the initial [225Ac]-FPI-1434 cycle: Sufficient target expression in at least 1 lesion following [111In]-FPI-1547 and SPECT imaging.
Exclusion Criteria:
Systemic therapeutic radiopharmaceutical within 6 months prior to enrollment into this study.
Contraindications to or inability to perform the required imaging procedures in this study (e.g., inability to lay flat during scan time)
Uncontrolled brain metastasis, including but not limited to the need for treatment with steroids, surgery or radiation therapy.
Anticancer therapy (including investigational agents) or external beam radiation therapy within 14 days of the dosing of [111In]-FPI-1547
Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast cancer, cervical cancer, prostate) that have undergone potentially curative therapy are not excluded.
Residual CTCAE ≥ Grade 2 side effects of prior therapy, with the exception of residual grade 2 alopecia.
Prior organ transplantation, including stem cell transplantation.
Any prior treatment with nitrosoureas or actinomycin-D.
Clinically relevant levels of protein in the urine
Known or suspected allergies or contraindications to the Investigational Products or any component of the investigational drug formulation.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
Received > 20 Gy prior radiation to large areas of the bone marrow [111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose, FPI-1175 Infusion, [225Ac]-FPI-1434 Injection single-dose, [111In]-FPI-1547 Injection, [225Ac]-FPI-1434 Injection multi-dose, FPI-1175 Infusion, [225Ac]-FPI-1434 Injection single-dose
Cancer
Clinics and Surgery Center (CSC), Phase I Clinic
MT2020-08 A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR0191 in subjects with Relapsed/Refractory Non-Hodgkin Lymphoma and r/r B-cell Acute Lymphoblastic Leukemia
To evaluate the safety and tolerability of PBCAR0191 in subjects with r/r B-ALL and r/r NHL and find an appropriate dose to optimize safety and efficacy. To evaluate the clinical benefit of PBCAR0191 in subjects with r/r B-ALL and r/r NHL. To evaluate the clinical activity of PBCAR0191 in subjects with r/r B-ALL and r/r NHL.
Joseph Maakaron
All
18 Years to old
Phase 1/Phase 2
STUDY00009953
STUDY00009953
Key Inclusion Criteria*
Criteria for B-ALL:
Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow cytometry, or a validated minimal residual disease assay.
Subjects with Philadelphia chromosome positive disease can be eligible if they are intolerant to tyrosine kinase inhibitor therapy or if they have r/r disease.
Criteria for NHL:
Subject has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding pathology report. Alternatively, if at least 1 tumor involved site is accessible at time of Screening, the subject's diagnosis is confirmed by pretreatment biopsy (excisional when possible) or by flow cytometry of fine needle aspirate. If a subject never had a CR, a sample from the most recent biopsy is acceptable. NHL subtypes included but are not limited to:
Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
FL including Grade 3 or transformed FL
High-grade B-cell lymphoma
Primary mediastinal lymphoma
Subject has measurable or detectable (for example positron emission tomography-positive) disease according to the Lugano Classification.
Subject must have received at least 2 prior chemotherapy-containing regimens, consistent with standard of care treatment guidance (e.g., NCCN), unless no second line therapy of known benefit exists for a given subject. Other than those specifically prohibited, other therapies are allowed until 7 days prior to initiation of LD. In that case, all Screening safety laboratories and disease assessments must be performed after the last dose of prior therapy. For Richter's transformation, only 1 prior line of therapy is required for the DLBCL component.
Subject has received no more than 7 systemic lines of anti-cancer therapy for the disease under study.
Subjects previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
Expansion cohort only: Subjects must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse.
Criteria for both B-ALL and NHL:
Eastern Cooperative Oncology Group performance status score of 0 or 1.
An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
Seronegative for human immunodeficiency virus antibody (i.e., intact immune function).
Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (calculated using the CKD-EPI equation [Levey et al, 2009]). If there is a concern that eGFR calculation is not an accurate reflection of renal function, a 24-hour urine collection for creatinine clearance may be used at the investigator's discretion.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal (ULN), unless there is suspected disease in the liver.
Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.
Platelet count ≥50,000/μL and absolute neutrophil count of ≥1000/ μL. Platelet transfusions within 14 days of screening are not allowed except for subjects in B-ALL disease cohort with extensive bone marrow disease burden, in which case adequate bone marrow recovery after prior treatment is required to be documented.
C-reactive protein (CRP) <2x ULN; subjects with CRP elevation within 2x ULN, ruling out infectious cause will be required.
Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition scan performed within 1 month before starting lymphodepleting chemotherapy. ECHO results performed within 6 months before Screening and at least 28 days after the last cancer treatment may be acceptable if the subject has not received any treatment with cardiotoxicity risks.
No clinically significant evidence of pericardial effusion or pleural effusion causing clinical symptoms and needing immediate intervention, based on the investigator's opinion. Any known effusion must be stable without need for drainage within 2 weeks of enrollment.
No clinically significant renal/pulmonary comorbidities.
Baseline oxygen saturation >92% on room air.
Key Exclusion Criteria*
Criteria for B-ALL:
Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
No active central nervous system (CNS) disease. Subjects with a history of CNS involvement must have a documented CR on at least 2 imaging studies at least 3 months apart (with no masses in parenchyma and no ocular involvement) and a negative cerebrospinal fluid cytology on at least 2 evaluations (one evaluation may be during the Screening Period and the other must be at least 3 months prior).
Criteria for NHL:
No prior or active CNS disease.
Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
Active hemolytic anemia.
Criteria for B-ALL and NHL:
Subject has had a malignancy, besides the malignancies of inclusion (B-ALL or NHL), that in the investigator's opinion, has a high risk of relapse in the next 2 years. In the case of Richter's transformation, subjects may be enrolled with ongoing chronic lymphocytic leukemia/small lymphocytic lymphoma.
Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection that has not resolved and does require therapeutic anti-microbial medications at least 7 days prior to LD. Subjects with elevated CRP must undergo infectious disease workup and the recommendations discussed with medical monitor to be considered on an individual basis. The CRP must be trending toward the normal range for the laboratory with the exception when it's deemed related to the underlying malignancy.
Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
Active hepatitis B or hepatitis C confirmed by PCR. Subject positive for inactive hepatitis B is allowed to enroll if on prophylactic treatment.
Subject is seropositive for hepatitis B antigen with confirmation. If confirmatory tests are negative, the subject can be enrolled.
Subject is seropositive for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, the subject must be tested for the presence of RNA by reverse transcription PCR and be hepatitis C virus-RNA negative.
Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the subject ineligible, including but not limited to:
Active ventricular or atrial dysrhythmia ≥ Grade 2, bradycardia ≥ Grade 2.
Myocardial infarction within 6 months before Screening.
Pulmonary embolism, deep vein thrombosis, or any other significant coagulopathy including disseminated intravascular coagulation.
History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening. In case of hypertensive crisis caused by omission of well-established treatment regimen, transient and promptly stabilized, enrollment must be discussed and agreed upon with sponsor and medical monitor.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
Presence of a CNS disorder that, in the opinion of the investigator, renders the subject ineligible for treatment.
Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject's safety.
History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding subjects needing steroids for physiologic replacement).
Subject has received stem cell transplant within 90 days before Screening.
Subject has active GvHD symptoms.
Subject has received systemic biologic agent for treatment of disease under study within 28 days of LD or other systemic anti-cancer therapy within 10 days of LD Note: this criterion does not apply if the subject has clear evidence of disease progression after such an agent has been administered and all AEs have resolved to a Grade 2 or less in severity. This should be discussed with the medical monitor for confirmation.
Participation in noninterventional registries or epidemiological studies is not excluded.
Radiotherapy within 4 weeks before Screening should be discussed with monitor and determined on a case-by-case basis.
Presence of pleural/peritoneal/pericardial catheter, as well as biliary and ureteral stents (does not apply to intravenous lines).
Subject has received live vaccine within 4 weeks before Screening. Non-live virus vaccines are not excluded.
Subject has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD.
Additional criteria apply
PBCAR0191, Fludarabine, Cyclophosphamide, PBCAR0191, Fludarabine, Cyclophosphamide
Non-Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia
PEPN2121 : A Phase 1/2 Study of Tiragolumab (NSC# 827799, IND# 161266) and Atezolizumab (NSC# 783608, IND# 161266) in Patients with Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that that has either come back (relapsed) or does not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, which is related to having more aggressive cancers that are harder to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Emily Greengard
All
12 Months to old
Phase 1/Phase 2
STUDY00017037
STUDY00017037
Inclusion Criteria:
Patients must be >= 12 months of age at the time of study enrollment. For part A, patients must be <18 years old at enrollment. For part B, there is no upper age limit
The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients <18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
Renal medullary carcinoma
Malignant rhabdoid tumor (extra-CNS)
Atypical teratoid rhabdoid tumor (CNS)
Poorly differentiated chordoma
Epithelioid sarcoma
Other SMARCB1 or SMARCA4 deficient tumors
Note: Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of > 50). Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell infusions (with or without total-body irradiation [TBI]):
Autologous stem cell infusion including boost infusion: >= 30 days
Cellular therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
External radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have had prior TIGIT targeting therapy
Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
Patients must not be receiving concomitant systemic steroid medications and > 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-alpha] agents) must have concluded >= 14 days prior to study enrollment
For patients with solid tumors without known bone marrow involvement
Peripheral absolute neutrophil count (ANC) >= 1000/uL (must be performed within 7 days prior to enrollment)
For patients with solid tumors without known bone marrow involvement
Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
Age; Maximum Serum Creatinine (mg/dL)
1 to < 2 years; Male: 0.6; Female: 0.6
2 to < 6 years; Male: 0.8; Female: 0.8
6 to < 10 years; Male: 1; Female: 1
10 to < 13 years; Male: 1.2; Female: 1.2
13 to < 16 years; Male: 1.5; Female: 1.4
>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance >= 70 mL/min/1.73 m^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
Patients with known Gilbert disease: Total bilirubin < 3 x ULN
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
Albumin >= 2 g/dL (must be performed within 7 days prior to enrollment)
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] v5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
International normalized ratio (INR) =< 1.5 (must be performed within 7 days prior to enrollment)
Serum amylase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
Serum lipase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
Grade 1 or lower calcium level
Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
Concomitant medications:
Corticosteroids:
Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
Patients who have undergone allogeneic bone marrow or stem cell transplant are not eligible
Patients with known, untreated CNS metastases will be excluded with the following exceptions:
Patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows no evidence for active disease in the CNS
Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
Patients who have active immune deficiency are not eligible
Patients who have known active tuberculosis are not eligible
Hepatitis B or C infection:
Patients < 18 years old at enrollment, who have known hepatitis B or C
Patients >= 18 years old at enrollment with:
Positive hepatitis B surface antigen (HBsAg), OR
Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) >= 500 IU/mL, OR
Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
Note: For adults (>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load
Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Atezolizumab, Biospecimen Collection, Computed Tomography, Fludeoxyglucose F-18, Magnetic Resonance Imaging, Positron Emission Tomography, Tiragolumab, X-Ray Imaging, Atezolizumab, Biospecimen Collection, Computed Tomography, Fludeoxyglucose F-18, Magnetic Resonance Imaging, Positron Emission Tomography, Tiragolumab, X-Ray Imaging
Atypical Teratoid/Rhabdoid Tumor, Epithelioid Sarcoma, Kidney Medullary Carcinoma, Malignant Solid Neoplasm, Poorly Differentiated Chordoma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Chordoma, Recurrent Epithelioid Sarcoma, Recurrent Kidney Medullary Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Rhabdoid Tumor, Refractory Atypical Teratoid/Rhabdoid Tumor, Refractory Chordoma, Refractory Epithelioid Sarcoma, Refractory Kidney Medullary Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Rhabdoid Tumor, Rhabdoid Tumor
ACNS1821: A Phase 1/2 Trial of Selinexor (KPT-330) and Radiation Therapy in Newly-Diagnosed Pediatric Diffuse Intrinsic Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
Christopher Moertel, MD
All
12 Months to 21 Years old
STUDY0016411
STUDY0016411
Inclusion Criteria:
STEP 0: Patients must be >= 12 months and =< 21 years of age at the time of enrollment on Step 0.
Please note:
This age range includes pre-screening for all HGG patients. Individual treatment protocols may have different age criteria.
Non-DIPG patients with tumors that do not harbor an H3K27M-mutation and are >= 18 years of age will not be eligible to enroll on ACNS1821 (Step 1).
STEP 0: Patient is suspected of having localized, newly diagnosed HGG, excluding metastatic disease, OR patient has an institutional diagnosis of DIPG
STEP 0:
For patients with non-pontine tumors: Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
For patients with DIPG: Patient and/or their parents or legal guardians have signed informed consent for ACNS1821.
STEP 0:
For patients with non-pontine tumors only, the specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 ASAP, preferably within 5 calendar days of definitive surgery
STEP 1: Patients must be >= 12 months and =< 21 years of age at the time of enrollment
STEP 1: Patients must have newly-diagnosed DIPG or HGG (including DMG).
STEP 1: Stratum DIPG
Patients with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2 weighted image, are eligible. No histologic confirmation is required.
Patients with pontine tumors that do not meet radiographic criteria for typical DIPG (e.g., focal tumors or those involving less than 2/3 of the pontine cross-sectional area with or without extrapontine extension) are eligible if the tumors are biopsied and proven to be high-grade gliomas (such as anaplastic astrocytoma, glioblastoma, high-grade glioma not otherwise specified [NOS], and/or H3 K27M-mutant) by institutional diagnosis.
STEP 1: Stratum DMG (with H3 K27M mutation)
Patients must have newly-diagnosed non-pontine H3 K27M-mutant HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
Note: Patients need not have either measurable or evaluable disease, i.e., DMG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment. For rare H3 K27M-mutant HGG in non-midline structures (e.g., cerebral hemispheres), these patients will be considered part of Stratum DMG.
STEP 1: Stratum HGG (without H3 K27M mutation)
Patients must have newly-diagnosed non-pontine H3 K27M-wild type HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
Please note:
Patients who fall in this category and who are >= 18 years of age are not eligible due to another standard-of-care regimen (radiation/temozolomide) that is available
Patients need not have either measurable or evaluable disease, i.e., HGG patients may have complete resection of their tumor prior to enrollment. Primary spinal tumors are eligible for enrollment
STEP 1: Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =<16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
STEP 1: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to step 1 enrollment)
STEP 1: Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to step 1 enrollment)
STEP 1: Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to step 1 enrollment)
STEP 1: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to step 1 enrollment) or
A serum creatinine based on age/gender as follows (within 7 days prior to step 1 enrollment):
Age / Maximum Serum Creatinine (mg/dL)
1 to < 2 years / male: 0.6; female: 0.6
2 to < 6 years / male: 0.8; female: 0.8
6 to < 10 years / male: 1; female: 1
10 to < 13 years / male: 1.2; female: 1.2
13 to < 16 years / male: 1.5; female: 1.4
>= 16 years / male: 1.7; female: 1.4
STEP 1: Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
STEP 1: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
STEP 1: Serum amylase =< 1.5 x ULN
STEP 1: Serum lipase =< 1.5 x ULN
STEP 1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
STEP 1: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
STEP 1: Patients must be enrolled and protocol therapy must begin no later than 31 days after the date of radiographic diagnosis (in the case of non-biopsied DIPG patients only) or definitive surgery, whichever is the later date (Day 0).
For patients who have a biopsy followed by resection, the date of resection will be considered the date of definitive diagnostic surgery. If a biopsy only was performed, the biopsy date will be considered the date of definitive diagnostic surgery.
Exclusion Criteria:
STEP 1: Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications.
STEP 1: Patients who are currently receiving another investigational drug are not eligible.
STEP 1: Patients who are currently receiving other anti-cancer agents are not eligible.
STEP 1: Patients >=18 years of age who have H3 K27M-wild type HGG.
STEP 1: Patients who have an uncontrolled infection.
STEP 1: Patients who have received a prior solid organ transplantation.
STEP 1: Patients with grade > 1 extrapyramidal movement disorder.
STEP 1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
STEP 1: Patients with metastatic disease are not eligible; MRI of spine with and without contrast must be performed if metastatic disease is suspected by the treating physician.
STEP 1: Patients with gliomatosis cerebri type 1 or 2 are not eligible, with the exception of H3 K27M-mutant bithalamic tumors.
STEP 1: Patients who are not able to receive protocol specified radiation therapy.
STEP 1:
Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
Lactating females are not eligible unless they have agreed not to breastfeed their infants. It is not known whether selinexor is excreted in human milk.
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
Sexually active patients of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control (including a medically accepted barrier method of contraception, e.g., male or female condom) for the duration of their study participation and for 90 days after the last dose of selinexor. Abstinence is an acceptable method of birth control. Biopsy, Magnetic Resonance Imaging, Radiation Therapy, Selinexor, Biopsy, Magnetic Resonance Imaging, Radiation Therapy, Selinexor
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Glioblastoma, Glioblastoma, Not Otherwise Specified, Malignant Glioma
PEPN2111 - A Phase 1/2 Trial of CBL0137 (NSC# 825802, IND# 155843) in Patients with Relapsed or Refractory Solid Tumors including CNS Tumors and Lymphoma
A Phase I/II trial of single agent intravenous CBL0137 in pediatric patients (≥ 12 months and ≤ 30 years) with relapsed/refractory solid tumors, including CNS tumors and lymphoma.
Emily Greengard
All
12 Months to 30 Years old
Phase 1/Phase 2
STUDY00015023
STUDY00015023
Inclusion Criteria:
Parts A and B1: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
Part B2 (relapsed/refractory osteosarcoma): Patients must be >= 12 months and =< 30 years of age at the time of study enrollment
Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
Part B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
Part B2: Patients with relapsed or refractory osteosarcoma
Part A: Patients must have either measurable or evaluable disease
Part B1 and B2: Patients must have measurable disease
Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Patients must have a Karnofsky or Lansky score >= 50%
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
Solid tumor patients: >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell Infusions (with or without total body irradiation [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 30 days
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Radiation therapy [XRT]/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have received prior exposure to CBL0137
For patients with solid tumors without known bone marrow involvement:
Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
For patients with solid tumors without known bone marrow involvement:
Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a creatinine based on age/gender as follows (performed within 7 days prior to enrollment unless otherwise indicated):
Age: Maximum serum creatinine (mg/dL)
1 to < 2 years: 0.6 (male); 0.6 (female)
2 to < 6 years: 0.8 (male); 0.8 (female)
6 to < 10 years: 1 (male); 1 (female)
10 to < 13 years: 1.2 (male); 1.2 (female)
13 to < 16 years: 1.5 (male); 1.4 (female)
>= 16 years: 1.7 (male); 1.4 (female)
Patients with solid tumors:
Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
Patients with solid tumors:
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
Shortening fraction of >= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated)
Ejection fraction of >= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
Corrected QT (QTC) < 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
Patients who are receiving drugs that prolong QTc are not eligible. QTc- prolonging drugs are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
Patients with known peripheral vascular disease are excluded
Patients with a history of pro-thrombotic disorder are not eligible
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible FACT Complex-targeting Curaxin CBL0137, FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Refractory Primary Malignant Central Nervous System Neoplasm
MT2005-25 Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
To determine the incidence of engraftment (defined as achieving donor derived neutrophil count >500/uL by day 42) in young children with leukemia or myelodysplastic syndrome undergoing a partially matched single unit umbilical cord blood transplant (UCBT) after a myeloablative preparative regimen consisting of busulfan, melphalan and fludarabine.
Christen Ebens
All
to 3 Years old
Phase 2
0511M77206
0511M77206
Inclusion Criteria:
Matched sibling donor (HLA 8/8), if available, or a unrelated partially HLA matched single unit based on the following priority:
1st priority: 4/6 matched unit, cell dose >5 x 10-7 nucleated cells/kg
2nd priority: 5/6 matched unit, cell dose > 4 x 10-7 nucleated cells/kg
3rd priority: 6/6 matched unit, cell dose > 3 x 10-7 nucleated cells/kg
Patients aged ≤ 3 years at diagnosis (not age of transplant) with hematological malignancy as detailed below:
Acute myeloid leukemia: high risk CR1 as evidenced by:
High risk cytogenetics t(4;11) or other MLL rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (>5 distinct changes); ≥ 2 cycles to obtain complete response (CR); CR2 or higher; Preceding myelodysplastic syndrome (MDS); All patients must be in CR or early relapse (i.e., <15% blasts in BM).
Acute lymphocytic leukemia: high risk CR1 as evidenced by: High-risk cytogenetic: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22); >1 cycle to obtain CR; CR2 or higher; All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
Persistent or rising minimal residual disease (MRD) after standard chemotherapy regimens: Patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy. MRD will be defined by either flow cytometry (>0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (PCR or FISH) or conventional cytogenetics (g-banding).
New Leukemia Subtypes: A major effort in the field of pediatric hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new high risk features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
Recipients must have a Lansky score ≥ 50% and have acceptable organ function defined as:
Renal: glomerial filtration rate > 60ml/min/1.73m^2
Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,
Pulmonary function: oxygen saturation >92%
Cardiac: left ventricular ejection fraction > 45%.
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
Exclusion Criteria:
Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).
History of HIV infection or known positive serology
Myeloablative transplant within the last 6 months.
Evidence of active extramedullary disease (including central nervous system leukemia). filgrastim, busulfan, cyclosporine, fludarabine phosphate, melphalan, mycophenolate mofetil, umbilical cord blood transplantation, filgrastim, busulfan, cyclosporine, fludarabine phosphate, melphalan, mycophenolate mofetil, umbilical cord blood transplantation
Leukemia, Myelodysplastic Syndromes, Childhood Acute Myeloid Leukemia in Remission, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Previously Treated Myelodysplastic Syndrome, Secondary Myelodysplastic Syndrome, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Excess Blasts, Refractory Anemia, De Novo Myelodysplastic Syndrome, Childhood Myelodysplastic Syndrome
MDS, AML
MT2013-31:Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis following Conditioning with Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
To evaluate the ability to achieve high-level donor hematopoietic engraftment (defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant) using related and unrelated BM, PBSC, or UCB grafts following a reduced intensity conditioning regimen based on targeted-exposure busulfan, fludarabine +/- serotherapy in patients with inherited metabolic disorders and severe osteopetrosis.
Paul Orchard
All
to 55 Years old
Phase 2
1406M51542
1406M51542
Inclusion Criteria:
0 through 55 years of age
Adequate graft available
Adequate organ function
Eligible Diseases:
Mucopolysaccharidosis Disorders:
MPS IH (Hurler syndrome)
MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
MPS VI (Maroteaux-Lamy syndrome)
MPS VII (Sly syndrome)
Glycoprotein Metabolic Disorders:
Alpha mannosidosis
Fucosidosis
Aspartylglucosaminuria
Sphingolipidoses and Recessive Leukodystrophies:
Globoid cell leukodystrophy
Metachromatic leukodystrophy
Niemann-Pick B patients (sphingomyelin deficiency)
Niemann-Pick C subtype 2
Peroxisomal Disorders:
Adrenoleukodystrophy with cerebral involvement
Zellweger syndrome
Neonatal Adrenoleukodystrophy
Infantile Refsum disease
Acyl-CoA-Oxidase Deficiency
D-Bifunctional enzyme deficiency
Multifunctional enzyme deficiency
Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)
Severe Osteopetrosis (OP)
Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)
Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other life-threatening, rare lysosomal, peroxisomal or other similar inherited disorders characterized by white matter disease or other neurologic manifestations for which there is rationale that transplantation would be of benefit, such as certain patients with Wolman's disease, GM1 gangliosidosis, I-cell disease, Tay-Sachs disease, Sandhoff disease or others.
Voluntary written consent
Exclusion Criteria:
Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days) Stem Cell Transplantation, IMD Preparative Regimen, Osteopetrosis Only Preparative Regimen, Osteopetrosis Haploidentical Only Preparative Regimen, cALD SR-A (Standard-Risk, Regimen A), cALD SR-B (Standard-Risk, Regimen B), cALD HR-D (High-Risk, Regimen C), cALD HR-D (High-Risk, Regimen D), Stem Cell Transplantation, IMD Preparative Regimen, Osteopetrosis Only Preparative Regimen, Osteopetrosis Haploidentical Only Preparative Regimen, cALD SR-A (Standard-Risk, Regimen A), cALD SR-B (Standard-Risk, Regimen B), cALD HR-D (High-Risk, Regimen C), cALD HR-D (High-Risk, Regimen D)
Mucopolysaccharidosis Disorders, Hurler Syndrome, Hunter Syndrome, Maroteaux Lamy Syndrome, Sly Syndrome, Alpha-Mannosidosis, Fucosidosis, Aspartylglucosaminuria, Glycoprotein Metabolic Disorders, Sphingolipidoses, Recessive Leukodystrophies, Globoid Cell Leukodystrophy, Metachromatic Leukodystrophy, Niemann-Pick B, Niemann-Pick C Subtype 2, Sphingomyelin Deficiency, Peroxisomal Disorders, Adrenoleukodystrophy With Cerebral Involvement, Zellweger Syndrome, Neonatal Adrenoleukodystrophy, Infantile Refsum Disease, Acyl-CoA Oxidase Deficiency, D-Bifunctional Enzyme Deficiency, Multifunctional Enzyme Deficiency, Alpha-methylacyl-CoA Racmase Deficiency, Mitochondrial Neurogastrointestingal Encephalopathy, Severe Osteopetrosis, Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS, CSF1R Mutation), Inherited Metabolic Disorders
Clinics and Surgery Center (CSC)
MT2015-25: Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
Ashish Gupta
All
to 30 Years old
Phase 2
1601M82901
1601M82901
Less than 30 years of age at diagnosis of neuroblastoma
End of Induction disease evaluation demonstrating CR, PR, MR or SD
Hematopoietic Recovery from last induction course of chemotherapy
No uncontrolled infection
Minimum frozen PBSCs of 2 x 10^6 CD34 cells/kg for each transplant are mandatory and a PBSC of 2 x 10^6 CD34 cells/kg for back-up are strongly recommended (thus, PBSC of no less than 6 x 10^6 CD34 cells/kg is encouraged). These must all be collected prior to the initiation of consolidation.
Adequate organ function defined as:
Hepatic: AST and ALT < 3 x upper limit of institutional normal; ALT ≤ 3 x ULN for age; total bilirubin ≤ 1.5 x ULN for age, if baseline was normal, > 1.0 1.5 x baseline if baseline was abnormal
Cardiac: shortening fraction ≥ 27% or ejection fraction ≥ 45%, no clinical congestive heart failure
Pulmonary: no evidence of dyspnea at rest and norequirement for supplemental oxygen
Renal: Creatinine clearance or GFR > 60 mL/min/1.73m^2. If a creatinine clearance is performed at end induction and the result is < 100 ml/min/1.73m^2, a GFR must then be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m^2
Recovery from acute toxicities of last cycle of induction chemotherapy
Appropriate written consent - adult or parent/guardian if patient is < 18 years of age and minor information sheet if patient is > 8 years of age
Thiotepa, Cyclophosphamide, Melphalan, Etoposide, Carboplatin, Autologous Stem Cell Infusion, Granulocyte colony stimulating factor, Thiotepa, Cyclophosphamide, Melphalan, Etoposide, Carboplatin, Autologous Stem Cell Infusion, Granulocyte colony stimulating factor
Neuroblastoma
High-risk neuroblastoma, Neuroblastoma, Myeloablative chemotherapy, Myeloablative consolidation chemotherapy, Autologous peripheral blood stem cell rescue, PBSC, Autologous stem cell rescue
COG AALL1621 - A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518, IND#133494) in Children and Young Adults with Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients (≥1 year and < 22 years ) with CD22 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. Immunotoxins, such as inotuzumab ozogamicin, are antibodies linked to a toxic substance and may help find cancer cells that express CD22 and kill them without harming normal cells.
Peter Gordon
All
1 Year to 21 Years old
Phase 2
STUDY00002494
STUDY00002494
Inclusion Criteria:
Patients must be >= 1 year and < 22 years of age at the time of enrollment
Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin [PE] is strongly recommended)
In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
Patients with one of the following:
Second or greater relapse;
Primary refractory disease with at least 2 prior induction attempts;
First relapse refractory to at least one prior re-induction attempt
Any relapse after HSCT (Cohort 1 ONLY)
Patients with Down syndrome are eligible ONLY for Cohort 1 with:
Any of above disease status, OR
First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, >= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.
Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
A serum creatinine based on age/gender as follows:
1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
>= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
Patients with any prior history of SOS irrespective of severity
Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
Patients who have been previously treated with inotuzumab ozogamicin
Patients who have previously received HSCT (Cohort 2 only)
Patients with Down syndrome (Cohort 2 only)
History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 (dose levels 1 and -1) if Erwinia formulation of asparaginase can be obtained
If Cohort 2 is enrolling at dose level -2, then patients who cannot receive asparaginase due to prior allergy, toxicity, or lack of access may enroll
NOTE: patients on AALL1621 are not eligible to co-enroll on AALL1931
Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
Patients who are currently receiving another investigational drug
Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
Patients who are currently receiving or plan to receive corticosteroids except as described below
Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
Patients who have an active uncontrolled infection defined as:
Positive bacterial blood culture within 48 hours of study enrollment;
Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
Active viral or protozoal infection requiring IV treatment
Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
Lactating females are not eligible unless they agree not to breastfeed their infants Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Calaspargase Pegol, Cyclophosphamide, Cytarabine, Diagnostic Imaging, Inotuzumab Ozogamicin, Leucovorin Calcium, Lumbar Puncture, Methotrexate, Pegaspargase, Vincristine, Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Calaspargase Pegol, Cyclophosphamide, Cytarabine, Diagnostic Imaging, Inotuzumab Ozogamicin, Leucovorin Calcium, Lumbar Puncture, Methotrexate, Pegaspargase, Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
Phase II trial of androgen deprivation therapy (ADT) and pembrolizumab for advanced stage androgen receptor-positive salivary gland carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111
We are looking at the effectiveness of adding an immunotherapy drug, pembrolizumab, to usual treatment for people who have salivary gland cancer that can’t be treated with surgery or radiation. The cancer must be androgen receptor positive.
Manish Patel
All
18 Years to old
Phase 2
STUDY00004710
STUDY00004710
Inclusion Criteria:
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
Locally advanced, recurrent, or metastatic salivary gland carcinoma that is not amenable to curative surgery or radiation
ECOG Performance Status of 0 or 1 within 28 days prior to registration.
Local, pathologic testing of androgen receptor-positive salivary gland carcinoma will be performed as standard of care. Archival tissue must be available for central confirmation of androgen receptor-positive disease and for correlative studies. AR positivity will be defined according to IHC staining of tumor tissue with at least 20% of tumor staining positive with moderate intensity (1+ or greater).
Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.
For patients who have been treated with prior therapy, patients must have documented progression of disease on their prior therapy for entry into the study.
Patients with prior chemotherapy, radiation, or surgery as part of curative intent therapy are allowed. Any number of prior lines of systemic therapy is permitted for entry into this study so long as prior therapy did not include anti-androgen therapy or immune checkpoint blockade.
If prior cancer treatment, the subject must have recovered from toxic effects of prior cancer treatment (other than alopecia) to ≤ Grade 1.
Adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
Absolute neutrophil count (ANC) ≥1500/µL
Platelets ≥100,000/µL
Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
Creatinine (Cr) OR Measured or calculated creatinine clearance (GFR can also be used in place of Cr or creatinine clearance) ≤1.5 × ULN OR
≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) o International normalized ratio (INR) OR prothrombin time (PT) & aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
A male participant must agree to use contraception during the treatment period and for at least 8 months after the last dose of study treatment and refrain from donating sperm during this period.
Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
Females of childbearing potential and males with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effect form of contraception from the time of informed consent until 8 months after treatment discontinuation.
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion Criteria:
Women of childbearing age with a positive serum pregnancy test within 72 hours prior to study registration.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
Has received prior androgen deprivation therapy including orchiectomy, gonadotropin-releasing hormone (GnRH) agonists/antagonists, androgen receptor blocker, abiraterone, or enzalutamide.
Has received prior systemic anti-cancer therapy including investigational agents within 14 days prior to registration.
Has had an allogenic tissue or solid organ transplant.
Has received prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities and require less than 10mg of prednisone (or equivalent corticosteroid) daily.
Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 14 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Has ≥Grade 3 hypersensitivity to pembrolizumab and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV).
Has a known history of active TB (Bacillus Tuberculosis).
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Goserelin Acetate, Pembrolizumab, Goserelin Acetate, Pembrolizumab
Salivary Gland Carcinoma
Clinics and Surgery Center (CSC)