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Zephyrus II: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects with Idiopathic Pulmonary Fibrosis (IPF)
This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of pamrevlumab in subjects with idiopathic pulmonary fibrosis (IPF).
Hyun Kim
All
18 Years and over
Phase 3
NCT04419558
STUDY00016379
Key
• Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines within the past 7 years prior to study participation.
• High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
• FVCpp value >45% and <95% at Screening and Day 1.
• Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90%.
• Previously treated with an approved IPF therapy (such as, pirfenidone or nintedanib) but discontinued at least 1 week prior to screening, unless neither treatment is available in the host country. Key
• Previous exposure to pamrevlumab.
• Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
• Female participants who are pregnant or nursing.
• Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study.
• Interstitial lung disease other than IPF.
• Sustained improvement in the severity of IPF.
• Other types of respiratory diseases that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study, including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
• Certain medical conditions, that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study (such as, myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or cancers).
• Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening.
• Recent use of any investigational drugs or unapproved therapies, or participation in any clinical trial.
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.
Inclusion Criteria:
• Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines within the past 7 years prior to study participation.
• High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
• FVCpp value >45% and <95% at Screening and Day 1.
• Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90%.
• Previously treated with an approved IPF therapy (such as, pirfenidone or nintedanib) but discontinued at least 1 week prior to screening, unless neither treatment is available in the host country. Key
Exclusion Criteria:
• Previous exposure to pamrevlumab.
• Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
• Female participants who are pregnant or nursing.
• Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study.
• Interstitial lung disease other than IPF.
• Sustained improvement in the severity of IPF.
• Other types of respiratory diseases that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study, including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
• Certain medical conditions, that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study (such as, myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or cancers).
• Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening.
• Recent use of any investigational drugs or unapproved therapies, or participation in any clinical trial.
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.
Drug: Pamrevlumab, Drug: Placebo
Idiopathic Pulmonary Fibrosis, Respiratory System
Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Lung Fibrosis, Clinics and Surgery Center (CSC), Idiopathic Pulmonary Fibrosis (IPF)
COG ADVL1521 - A Phase 2 Study of the MEK inhibitor Trametinib (IND #119346, NSC# 763093) in Children with Relapsed or Refractory Juvenile Myelomonocytic Leukemia
This phase II trial studies how well trametinib works in treating patients (≥ 2 years and < 22 years of age) with juvenile myelomonocytic leukemia that has come back or does not respond to treatment. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Emily Greengard
All
1 Month to 21 Years old
Phase 2
NCT03190915
STUDY00003883
Inclusion Criteria:
• Patients must be >= 1 month and < 22 years of age at the time of study entry
• Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria
• JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis
• Splenomegaly
• > 1000 (1 x 10^9/uL) circulating monocytes
• < 20% blasts in the bone marrow or peripheral blood
• Absence of the t(9;22) or BCR/ABL fusion gene
• JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
• Somatic mutation in RAS or PTPN11
• Clinical diagnosis of NF1 or NF1 gene mutation
• Homozygous mutation in CBL
• Monosomy 7
• JMML category 3 (at least two of the following if no category 2 criteria are met):
• Circulating myeloid precursors
• White blood cell count, > 10 000 (10 x 10^9/ uL)
• Increased hemoglobin F for age
• Clonal cytogenetic abnormality
• GM-CSF hypersensitivity
• Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 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
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
• Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
• Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy
• Hematopoietic growth factors: at least 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
• Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibodies:
• At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
• Radiotherapy:
• >= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)
• >= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received
• >= 4 weeks must have elapsed if other substantial bone marrow irradiation was given
• Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion
• Patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male) 0.4 (female)
• 6 months to < 1 year: 0.5 (male) 0.5 (female)
• 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)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA)
• Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs
• Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed
Exclusion Criteria:
• Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus
• Concomitant Medications
• Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 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
• Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid
• 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 (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
• Anti-graft versus host disease (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
• Cardiac medications: any medications for treatment of left ventricular systolic dysfunction
• Patients who have an uncontrolled infection 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
• Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible
• Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
• Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension
• Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =< the 95th percentile for age, height, and gender
• Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible
• Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll
Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: Trametinib
Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1
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
up to 24 Months old
Phase 1/Phase 2
NCT04411654
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.
Biological: LY3884961, Drug: Methylprednisolone, Drug: Sirolimus, Drug: Prednisone
Gaucher Disease, Type 2
Gaucher Disease, GD, Gaucher, Type 2 Gaucher, Neuronopathic Gaucher, nGD, AAV9, GBA, Gene Therapy, Glucocerebrosidase, GBA1 mutation, Infants
MT2018-35 A Randomized Phase 2 Study of Obinutuzumab for Prevention of Chronic Graft vs. Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation
This is a prospective, multicenter, randomized phase II trial of prophylactic obinutuzumab vs. placebo for prevention of chronic Graft vs. Host Disease (cGVHD) after Hematopoietic Cell Transplantation (HCT). A single dose of obinutuzumab or placebo will be administered prophylactically at 3, 6, 9 and 12 months after HCT. Clinical and immunological endpoints are measured sequentially. 200 subjects will be randomized and analyzed in a modified intention-to-treat fashion. The primary objective is to determine the effect of obinutuzumab prophylaxis on the incidence of corticosteroid-requiring cGVHD after allogeneic HCT. The primary endpoint of this phase II trial is the rate of corticosteroid-requiring cGVHD one year after HCT.
Najla El Jurdi
Phase II
NCT02867384
STUDY00005258
Graft vs. Host Disease
Clinics and Surgery Center (CSC), Graft vs. Host Disease
STRIKE-PE: A Prospective, Multicenter Study of the IndigoTM Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism
The purpose of this study is to collect information on how patients with PE recover after treatment with the Indigo Aspiration System. The Indigo Aspiration System is a medical device that has been cleared by the U.S. Food and Drug Administration (FDA) for removing blood clots from the blood vessels throughout the body, excluding the head. The device is commercially available globally. Participants will be in this research study for about one year. Participants will be asked to complete a screening and baseline visit, device procedure in-patient visit as part of routine treatment for their PE, one post-procedure visit in the hospital and two follow-up visits. The study team will collect information on tests and procedures done during these visits from their medical records. They will also be asked to complete a quality of life questionnaire.
Michael Rosenberg
Post Market Monitoring
NCT04798261
STUDY00013412
Pulmonary Embolism
A Research Study of How Well Macimorelin Works to Find Out if Children Have a Lack of Growth Hormone and How Safe it is (DETECT)
The researchers are doing this study to help children and teenagers with suspected growth hormone deficiency to be able to get only one stimulation test in the future instead of two stimulation tests, as it is standard now. This one stimulation test would be the new macimorelin study test. This stimulation study test has been approved as a test on diagnosing growth hormone deficiency in adults. It is being tested in clinical trials in pediatric participants and its use in this study is investigational because it has not been approved for use in children.
All
2 Years to 17 Years old
Phase 3
NCT04786873
Inclusion Criteria:
• Informed consent of subject, parent(s) or legally acceptable representative (LAR) of subject and child assent, if appropriate, must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Male and female pediatric subjects from 2 to less than 18 years of age at the time of signing informed consent.
• Indication for the performance of growth hormone stimulation test.
• Presence of a height measurement minimum 6 and maximum 18 months prior to screening.
Exclusion Criteria:
• Established diagnosis of a disease that is sufficient to explain growth deficiency or metabolic disorders that are also associated with short stature (e.g., Turner syndrome, skeletal dysplasia's, celiac disease, etc.).
• Ongoing growth hormone therapy.
• Presence of hypothyroidism and/or adrenal insufficiency without adequate and stable replacement therapy treatment for at least 30 days prior to first GHST.
• Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g., somatostatin analogues, clonidine, levodopa and dopamine agonists) or provoking the release of somatostatin (antimuscarinic agents e.g., atropine).
• Medical history of ongoing clinically symptomatic psychiatric disorders.
• 2nd or 3rd degree atrioventricular-block, prolongation of the QRS complex over 120 milliseconds, prolongation of the QTc interval over 450 milliseconds, or any other clinically significant abnormal electrocardiogram results at the V2 pre-dose electrocardiogram (ECG) as judged by the investigator.
• Previous participation in this trial. Participation is defined as signed informed consent.
• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
• Known or suspected hypersensitivity to trial product(s) or related products;
• Any disorder, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
• Concomitant treatment with any drugs that might prolong QT/QTc Note: A subject who receives such treatment will not be a candidate for this study, if his/her condition does not allow for a treatment-free period of at least 5 elimination half-lives of the drug that might prolong QT/QTc before the GHST;
• Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (aspartate amino transferase (AST), alkaline phosphatase (ALT), gamma-glutamyl transferase (GGT) > 2.5 x upper limit of normal (ULN); creatinine or bilirubin > 1.5x ULN);
• Current active malignancy other than non-melanoma skin cancer;
• Female of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
• Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
• Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative;
• Anticipated non-availability for trial visits/procedures.
Drug: Macimorelin, Diagnostic Test: Arginine, Diagnostic Test: Clonidine
Growth Hormone Deficiency
childhood-onset growth hormone deficiency, diagnosis of growth hormone deficiency, diagnosis of childhood-onset growth hormone deficiency, diagnostic test for growth hormone deficiency
A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients with Recurrent Small Cell Lung Cancer: Big Ten Cancer Research Consortium BTCRC-LUN17-127
We are studying the effectiveness and side effects of a drug, plinabulin when added to the usual immunotherapy used to treat people who have small cell lung cancer that has recurred.
Naomi Fujioka
All
18 Years and over
Phase 1/Phase 2
NCT03575793
STUDY00004593
Inclusion Criteria:
The patients must satisfy all of the following inclusion/exclusion criteria in order to be
eligible for the study:
• Must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines.
• Males and females aged >18 years at time of consent.
• Histological or cytological confirmed extensive-stage SCLC
• Patients who progressed after at least 1 platinum-based chemotherapy regimen. Patients with platinum resistance (defined as recurrence or progression of disease within 90 days of completion of the platinum-based regimen) are eligible. For phase II, patients also must have been treated with at least one prior line of PD-1/PD-L1 therapy.
• Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before registration and minimum life expectancy of at least 12 weeks.
• Treatment to be initiated at least 2 weeks since last dose of prior systemic anticancer therapy (chemotherapy, radiation, and/or surgery.
• Recovery to grade 1 of any clinically significant toxicity (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy) prior to initiation of study drugs.
• Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti estrogens, or ovarian suppression.
• Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within 14 days of study registration and within the 24-hour period prior to the first dose of study drug.
• Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 23 weeks after their last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.
• For male patients who are sexually active and who are partners of premenopausal women: agreement to use 2 forms of contraception as in criterion 9b above during the treatment period and for 31 weeks after the last dose of study drug.
• Adequate laboratory values.
• Absolute neutrophil count ≥1,000/µL
• Platelet count ≥100,000/µL
• Hemoglobin ≥9.0 g/dL
• Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for subjects with Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN if evidence of hepatic involvement by malignant disease)
• Creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR) ≥40 mL/min/1.73m2
• Lipase and Amylase ≤1.5 x ULN. Subjects with Lipase >1.5 x ULN may enroll if there are neither clinical nor radiographic signs of a pancreatitis. Exclusion Criteria Patients with any of the following will be excluded from participation in the study.
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids. Prior history of radiation pneumonitis is allowed if pneumonitis was restricted to the field of radiation.
• History of ileus or other significant gastrointestinal disorder known to increase the risk of ileus or chronic bowel hypomotility
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks (female) or 31 weeks (male) after the last dose of study drug.
• Must not have received CTLA-4 targeted therapy previously
• Treatment with any investigational agent within 28 days prior to registration for protocol therapy. Vaccination for SARS-CoV-2 is allowed as well as any therapy as required for the treatment of active COVID 19 infection.
• Known active symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis. Patients whose brain metastases have been treated may participate provided there is no evidence of progression for at least 2 weeks after CNS-directed treatment, as ascertained by clinical examination or brain imaging.
• Known history of human immunodeficiency virus (HIV) or active hepatitis B (by surface antigen expression or polymerase chain reaction [PCR]) or active hepatitis C (by PCR) infection. NOTE: HIV testing is not required; Hepatitis B and C testing are required at screening.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration.
• 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) or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo, alopecia, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, celiac disease controlled by diet alone or conditions not expected to recur in the absence of an external trigger are permitted.
• A condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to administration of study drugs.
• History of psychiatric illness or social situations that would limit compliance with study requirements. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Prior malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry.
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to their first dose of study drugs.
• Evidence of ongoing inadequately controlled hypertension (defined as baseline systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg).
• Any active grade 3 or higher viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drugs. Routine antimicrobial prophylaxis is permitted.
Drug: Nivolumab, Drug: Plinabulin, Drug: Ipilimumab
Lung Cancer, SCLC
Clinics and Surgery Center (CSC)
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects with Classic Congenital Adrenal Hyperplasia
Study SPR001-203 will be a larger, randomized, double-blind, placebo-controlled, dose-ranging study that will investigate the efficacy and safety of up to 52 weeks of treatment with tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline (A4 >1.5x upper limit of normal [ULN] and ACTH >2x ULN) on their current Glucocorticoid regimen.
Kyriakie Sarafoglou
Phase III
NCT04457336
STUDY00009488
Congenital Adrenal Hyperplasia
Adrenal Disorder, CAH, Congenital Adrenal Hyperplasia
MT2021-14 A PHASE I/II, DOSE-ESCALATION STUDY OF MGTA-117 IN PATIENTS WITH ADULT ACUTE MYELOID LEUKEMIA (AML) AND MYELODYSPLASIA-EXCESS BLASTS (MDS-EB)
The overall objective of this study is to investigate the safety, tolerability, PK, PD, and potential anti-leukemia activity of MGTA-117 given intravenously (IV) as a single dose in adults with R/R AML or MDS-EB. Once adequate data are available, the protocol will be amended to assess the safety/tolerability and preliminary efficacy of MGTA-117 in combination with reduced intensity conditioning (RIC) in patients with AML who are proceeding to HSCT.
Mark Juckett
All
18 Years to 75 Years old
Phase 1
NCT05223699
STUDY00013345
Inclusion Criteria:
• Participant must have a World Health Organization (WHO)-defined diagnosis of R/R AML and meet one of the following criteria:
• The participant has experienced primary AML induction failure or R/R AML OR
• The participant has a WHO-defined diagnosis of MDS-EB and has failed/is refractory to HMA OR
• Presence of MRD in morphologic CR
• CD117+ based on IHC or flow cytometry
• Participant must have an identified HSC donor (related donor or unrelated donor), haplo-identical transplant donor, or umbilical blood donor.
• Participant's Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.
• Participant must have adequate baseline hepatic function. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤2 x upper limit of normal (ULN), and serum bilirubin ≤1.5 x ULN.
• Estimated creatinine clearance ≥60 mL/min
• Adequate cardiac function as demonstrated by cardiac left ventricular ejection fraction ≥40% or perform New York Heart Association (NYHA) classification I and II
Exclusion Criteria:
• Acute promyelocytic leukemia (APL).
• Known active central nervous system (CNS) leukemia or chloroma (granulocyte sarcoma).
• Received HSCT within 6 months prior to dosing
• Received chimeric antigen-receptor cell therapies within 6 months prior to dosing
• Has active graft-versus-host disease (GVHD).
• Active hepatitis B (Hep-B) or hepatitis C (Hep-C) infection or history of human immunodeficiency virus (HIV).
• Participant with a QTc value >470 msec
• Participant has received another investigational drug or device within 14 days or 5 half-lives of dosing, whichever is longer.
• Participant has any clinically significant medical condition, which in the opinion of the Investigator may place the participant at an unacceptable risk.
• Active uncontrolled systemic bacterial, fungal, or viral infection
• Participant has a history of serious allergic reactions, which in the opinion of the Investigator may pose an increased risk of serious infusion reactions.
• Participant has had any systemic antileukemia treatment within 14 days except hydroxyurea, which is permitted until 24 hours prior to MGTA-117 dosing.
• Participant has received prior anti-CD117 antibody treatment.
• Participant has received gemtuzumab ozogamicin (Mylotarg) within the last 3 months prior to dosing.
• Participant has received recent monoclonal antibody as anti-leukemic therapy within the last 30 days or 5 half-lives, whichever is longer.
• Participant has received recent vaccination within the last 14 days prior to dosing.
• Participant has Grade 2 or higher electrolyte abnormality at screening
Biological: MGTA-117
Acute Myeloid Leukemia, Myelodysplasia
Acute Myeloid Leukemia, Myelodysplasia-Excess Blasts, MGTA-117, Hematopoietic stem cell transplant, Clinics and Surgery Center (CSC)
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Rosnilimab (ANB030) in the Treatment of Subjects with Alopecia Areata
This research is studying a new treatment, rosnilimab, in a small number of people to learn about the safety, potential effect on alopecia areata, and how it interacts with the body. Researchers want to understand if rosnilimab may cause hair regrowth in people with alopecia areata and how it may work.
Maria Hordinsky
18 Years and over
Phase II
NCT05205070
STUDY00014901
Inclusion Criteria:
Men and women, adults 18- 65 years of age who are in good health
Diagnosed with severe or very severe Alopecia Areata and have greater than or equal to 50% scalp hair loss
Must be willing to stop using other types of medications to treat Alopecia Areata throughout the study
Attend 10 visits over 28 weeks
Other requirements, which the study team will review with you
Exclusion Criteria:
Subjects cannot participate in this study if they have another cause of hair loss in addition to alopecia areata. Subjects also cannot participate if they have had surgery in the last 4 weeks, if immune
system is compromised, if are allergic to anything in rosnilimab, if recently used a
prescription treatment for alopecia areata, if have tuberculosis, if person is pregnant or breastfeeding, or if person intends to become pregnant while part of this study. Subjects cannot
participate in this study if they are currently part of another study that is using an experimental drug or device (medical tool). Alopecia Areata, Dermatology (Skin, Hair & Nails), Immune Diseases
hair loss, Alopecia areata, PD-1 receptor, Rosnilimab
HM2017-39 Phase III Randomized Study of Crenolanib versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects with FLT3 Mutated Acute Myeloid Leukemia
This study is meant to compare the efficacy of crenolanib with midostaurin administered following induction chemotherapy and consolidation therapy on event-free survival (EFS) in newly diagnosed acute myeloid leukemia subjects with FLT3 mutation.
Mark Juckett
All
18 Years to 60 Years old
Phase 3
NCT03258931
STUDY00002581
Inclusion Criteria:
• Confirmed diagnosis of de novo AML according to World Health Organization (WHO) 2016 classification
• Presence of FLT3-ITD and/or D835 mutation(s) in bone marrow or peripheral blood
• Age ≥ 18 years and ≤ 60 years
• Adequate hepatic function within 48 hours prior to induction chemotherapy
• Adequate renal functions within 48 hours prior to induction chemotherapy
• ECOG performance status within 48 hours prior to induction chemotherapy ≤ 3
• Eligible for intensive cytarabine/daunorubicin (7+3) chemotherapy specified
Exclusion Criteria:
• Acute promyelocytic leukemia (APL)
• Known clinically active central nervous system (CNS) leukemia
• Severe liver disease
• Active infections
• Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Known infection with human immunodeficiency virus (HIV)
• Prior systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents)(except for hydroxyurea and/or leukapheresis)
Drug: Crenolanib, Drug: Midostaurin, Drug: Cytarabine, Drug: Duanorubicin
Newly Diagnosed FLT3 Mutated AML
Clinics and Surgery Center (CSC)
MT2021-11: An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects with Epstein-Barr Virus-associated Diseases
This study is intended to determine the clinical benefit of tabelecleucel (EBV-specific cytotoxic T-lymphocytes) in subjects with EBV-associated diseases.
Joseph Maakaron
All
Not specified
Phase 2
NCT04554914
STUDY00013494
Inclusion Criteria:
• Diagnosis of EBV+ disorder
• Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from 1 year to < 16 years
• Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator Cohort-specific
Inclusion Criteria:
• For participants with PID LPD:
• Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
• Participant must have systemic measurable disease and/ or CNS measurable disease
• Definitive therapy (eg, allogeneic HCT, gene therapy) for the underlying PID is planned
• Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
• For participants with AID LPD:
• Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF
• Participant must have systemic measurable disease and/ or CNS measurable disease
• Participants who are human immunodeficiency virus positive (HIV+) must meet both of the following criteria: Have an HIV viral load assessed by reverse transcription-polymerase chain reaction (RT-PCR) below the lower limit of detection and CD4 >= 50 cells/μL within 6 months prior to the first dose of tabelecleucel
• Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
• For participants with CNS PTLD:
• Newly diagnosed or relapsed/refractory EBV+ CNS PTLD histologically confirmed by biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
• Participant may have systemic and CNS disease or CNS disease only
• Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
• For participants with EBV+ PTLD, where standard first line therapy (rituximab and/or chemotherapy) is not appropriate, including CD20-negative disease:
• Newly diagnosed, biopsy-proven EBV+ PTLD
• Ineligible for standard first-line therapy for EBV+ PTLD, as determined by the investigator
• Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used.
• For participants with sarcoma, including LMS:
• Newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma. Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ sarcoma, as determined by the investigator.
• Biopsy-proven EBV+ sarcoma
• Measurable disease using diagnostic PET/CT and/or MRI following RECIST 1.1 criteria
• For participants with CAEBV:
• Newly diagnosed or previously treated CAEBV
• Detectable EBV viremia on at least 2 occasions at a minimum of 90 days apart
• At least 3 active clinical findings (per Kimura H, et al. Front Immunol. 2017;8:1867) as: Fever >= 38.5°C; splenomegaly, lymphadenopathy, and/or hepatomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypogammaglobulinemia; hemophagocytosis; hepatitis; neuropathy; rash; and hydroa vacciniforme
• For participants with EBV+ viremia with HLH:
• Newly diagnosed or previously treated EBV+ viremia with HLH
• A molecular diagnosis consistent with HLH-2004 trial (per Henter JI, et al. Pediatr Blood Cancer. 2007;48:124-31) OR 5 or more of the clinical symptoms (per Jordan MB, et al. Blood. 2011;118:4041-4052): Fever >= 38.5°C; splenomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypertriglyceridemia (fasting >= 265 mg/dL) and/or hypofibrinogenemia (<= 150 mg/dL); hemophagocytosis in bone marrow, spleen, lymph nodes, or liver; low or absent natural killer cell (NK-cell) activity; ferritin >= 500 ng/mL; and elevated soluble CD25
Exclusion Criteria:
• Burkitt, T-cell (except in the setting of HLH), natural killer/T-cell lymphoma/LPD, Hodgkin, or transformed lymphoma
• Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment
• Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
• Need for vasopressor or ventilatory support
• Prior therapy (in order of increasing washout period) prior to enrollment as:
• Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
• Within <= 8 weeks for cellular therapies (EBV-CTLs, chimeric antigen receptor therapies directed at T cells or T-cell subsets, donor lymphocyte infusion, other CTLs); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
• Unwilling to use protocol specified contraceptive methods
• Women who are pregnant or breastfeeding
• Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
• For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant
Biological: Tabelecleucel
Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (PID LPD), EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (AID LPD), EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (CNS PTLD), EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications, EBV+ Sarcomas, Leiomyosarcoma, Chronic Active Epstein-Barr Virus (CAEBV), Chronic Active Epstein-Barr Virus With Hemophagocytic Lymphohistiocytosis (HLH), Lymphohistiocytosis, Hemophagocytic
Clinics and Surgery Center (CSC), Allogeneic, Off-The-Shelf T-cell Immunotherapy, Epstein-Barr Virus (EBV), Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL), Solid Organ Transplant (SOT), Hematopoietic Cell Transplant (HCT)
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 and over
Phase 1
NCT05322408
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
• 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
Drug: HCW9218
Solid Tumor
Clinics and Surgery Center (CSC), Phase I Clinic
A Randomized Phase II Study Comparing Single-Agent Olaparib, Single Agent Cediranib, and the Combination of Cediranib/Olaparib in Women with Recurrent, Persistent or Metastatic Endometrial Cancer
To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms that may be added by subsequent amendment) versus single agent cediranib as measured by progression free survival (PFS), in patients with recurrent, persistent or metastatic endometrial cancer.
Phase II
NCT03660826
0123456789
Endometrial Undifferentiated Carcinoma, Endometrioid Adenocarcinoma, Recurrent Endometrial Serous Adenocarcinoma, Recurrent Uterine Corpus Cancer, Stage IV Uterine Corpus Cancer AJCC v7, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (PSMAddition)
To evaluate radiographic progression free survival in patients with mHSPC receiving Standard of Care and 177Lu-PSMA-617 versus patients receiving Standard of Care without 177Lu-PSMA-617.
Emmanuel Antonarakis
Male
18 Years and over
Phase 3
NCT04720157
STUDY00015038
Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
• Signed informed consent must be obtained prior to participation in the study
• Patients must be adults ≥18 years of age
• Patients must have an ECOG performance status of 0 to 2
• Patients must have a life expectancy >9 months as determined by the study investigator
• Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
• Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
• Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization:
• Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR
• Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR
• Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).
• Patients must have adequate organ function:
• Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
• Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
• Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
• Albumin ≥2.5 g/dL
• Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
• Patients must be: Treatment naïve OR minimally treated with:
• Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
• If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
• Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.
Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for inclusion in this
study.
• Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
• Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).
• Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy
• Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed
• Ongoing participation in any other clinical trial
• Use of other investigational drugs within 30 days prior to day of randomization
• Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
• Transfusion for the sole purpose of making a participant eligible for study inclusion
• Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible.
• Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance).
• Active clinically significant cardiac disease defined as any of the following:
• NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
• History of familial long QT syndrome or known family history of Torsades de Pointes
• Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• Any condition that precludes raised arms position
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
Drug: 177Lu-PSMA-617, Drug: 68Ga-PSMA-11, Drug: ARDT, Drug: ADT
Prostatic Neoplasms
Lutetium-177 PSMA-617, 177Lu-PSMA-617, Androgen receptor-directed therapy, ARDT, Androgen Deprivation Therapy, ADT, Metastatic Hormone sensitive prostate cancer, mHSPC, Radiographic progression free survival, rPFS, Prostate-specific membrane antigen, PSMA, Gallium-68 PSMA-11, 68Ga-PSMA-11, Radioligand Therapy, RLT, Clinics and Surgery Center (CSC)
PANOVA-3: Pivotal, randomized, open-label study of Tumor Treating Fields (TTFields, 150kHz) concomitant with gemcitabine and nab-paclitaxel for front-line treatment of locally-advanced pancreatic adenocarcinoma
Adult patients with locally advanced, unresectable pancreatic carcinomas will be screened at baseline, and randomized 1:1 to treatment in either of two arms: standard-of-care palliative chemotherapy using gemcitabine + nab-paclitaxel (given on days 1, 8, and 15 of each 28-day cycle), or the same chemotherapeutic regimen with the addition of alternating electric tumor-treating fields (TTFields) applied to the patients abdominal cavity using pads attached to a source pack. The TTFields are applied 24 hours per day/7 days per week. Follow-up CT scans will be performed every 8 weeks, as is standard of care, with post-progression follow-up visits and survival follow-up visits every four weeks.
Emil Lou
All
18 Years and over
Phase 3
NCT03377491
STUDY00004177
Inclusion Criteria:
• 18 years of age and older
• Life expectancy of ≥ 3 months
• Histological/cytological diagnosis of de novo adenocarcinoma of the pancreas
• Unresectable, locally advanced stage disease according to the following criteria:
• Head/uncinate process:
• Solid tumor contact with SMA>180°
• Solid tumor contact with the CA>180°
• Solid tumor contact with the first jejunal SMA branch
• Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)
• Contact with most proximal draining jejunal branch into SMV
• Body and tail
• Solid tumor contact of >180° with the SMA or CA
• Solid tumor contact with the CA and aortic involvement
• Unreconstructible SMV/PV due to tumor involvement or occlusion (can be d/t tumor or bland thrombus)
• No distant metastasis, including non-regional lymph node metastasis
• No borderline resectable (per Al-Hawary MM, et al., Radiology 201414)
• ECOG score 0-2
• Amenable and assigned by the investigator to receive therapy with gemcitabine and nab-paclitaxel
• Able to operate the NovoTTF-100L(P) System independently or with the help of a caregiver
• Signed informed consent form for the study protocol
Exclusion Criteria:
• Prior palliative treatment (e.g. surgery, radiation) to the tumor
• Cancer requiring anti-tumor treatment within the 5 years before inclusion, excluding treated stage I prostate cancer, in situ cervical or uterus cancer, in situ breast cancer and non-melanomatous skin cancer.
• Serious co-morbidities:
• Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x Upper Limit of Normal (ULN); AST and/or ALT > 2.5 x ULN; and serum creatinine > 1.5 x ULN.
• History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
• History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial.
• History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable.
• Active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol therapy.
• History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent.
• Concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel
• Implantable electronic medical devices in the torso, such as pacemakers
• Known severe hypersensitivities to medical adhesives or hydrogel, or to one of the chemotherapies used in this trial.
• Pregnancy or breast-feeding (female patients with reproductive potential and their partners must accept to use effective contraception throughout the entire study period and for 3 months after the end of treatment). All patients who are capable of becoming pregnant must take a pregnancy test which is negative within 72 hours before beginning treatment. The definition of effective contraception is left up to the decision of the investigator.
• Unable to follow the protocol for medical, psychological, familial, geographic or other reasons.
• Admitted to an institution by administrative or court order.
Device: NovoTTF-100L(P), Drug: Gemcitabine, Drug: nab paclitaxel
Pancreas Adenocarcinoma
Locally Advanced Pancreatic Adenocarcinoma, TTFields, Tumor Treating Fields, Gemcitabine, nab-Paclitaxel, Minimal toxicity, TTF, Novocure, Clinics and Surgery Center (CSC)
OMS721-IGA-001: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of the Safety and Efficacy of OMS721 in Patients with Immunoglobulin A (IgA) Nephropathy (ARTEMIS - IGAN)
This is a Phase 3, double-blind, randomized, placebo-controlled, study in patients aged 18 years and above with a biopsy-confirmed diagnosis of IgAN and with 24-hour UPE that is > 1 g/day at baseline. During the study, all patients will continue optimized renin-angiotensin system (RAS) blockade. The study consists of five periods: Screening, Run-In, Initial Treatment (Weeks 1-12), Response Evaluation (Weeks 13-24), and Follow-Up (Weeks 25 to end-of-study). The study duration for each patient is expected to last up to 160 weeks.
Patrick Nachman
All
18 Years and over
Phase 3
NCT03608033
STUDY00002971
Inclusion Criteria:
• Age 18 years or older at the onset of Screening
• Biopsy confirmed diagnosis of IgAN within 8 years prior to Screening
• Proteinuria of > 1 g/day within 6 months prior to Screening or uPCR > 0.75 by spot urine at Screening
• Mean of two proteinuria measurements > 1 g/day at baseline
• Estimated glomerular filtration rate of ≥ 30 mL/min/1.73 m2 at Screening and baseline
Exclusion Criteria:
• Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), or cytotoxic drugs, for IgA within 8 weeks prior to Screening. Treatment with immunosuppressants or cytotoxic drugs for IgAN is not allowed during the Run-In Period. Treatment with immunosuppressants are allowed if such treatment is for indications other than IgAN.
• Treatment with eculizumab within 8 weeks prior to Screening. Treatment with eculizumab is not allowed during the Run-In Period.
• Treatment with systemic corticosteroids within 8 weeks prior to Screening. Treatment with systemic corticosteroids is not allowed during the Run-In Period.
• Uncontrolled BP, a systolic BP of > 150 mmHg and a diastolic BP of > 100 mmHg at rest despite the combination of two or more anti-hypertensives including ACEIs, ARBs, or direct renin inhibitors at Screening and baseline
• Female patients who are pregnant, breast feeding, or planning to become pregnant up through 12 weeks after the last dose of study drug, including possible retreatments
• Clinical or biological evidence of Type 1 diabetes mellitus (DM), or poorly controlled DM with hemoglobin A1c > 7.5 or with evidence of diabetic nephropathy on biopsy, systemic lupus erythematosus, IgA vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease during Screening and Run-In
• History of renal transplantation
• Have a known hypersensitivity to any constituent of the investigational product
• Rapidly progressive glomerulonephritis
• Significant abnormalities in clinical laboratory values
• History of human immunodeficiency virus (HIV), evidence of immune suppression, active HCV infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), HBV infection (patients with positive HBsAg are excluded. For patients with isolated positive anti-HBc antibody, HBV DNA test by PCR must be non-detectable to enroll).
• Diagnosis of a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease-free for ≥ 5 years
• Have received any other investigational drug or device or experimental procedures within 30 days of the Screening Visit (SV)
Biological: OMS721, Other: Vehicle (D5W or saline)
IgA Nephropathy
Clinics and Surgery Center (CSC)
A Randomized, Parallel-Arm, Active Control, Multicenter Study Assessing the Safety and Efficacy of DEXTENZA for the Treatment of Ocular Pain and Inflammation Following Surgery for Pediatric Cataract
This randomized trial will compare the insertion of a DEXTENZA plug versus the standard prednisolone acetate suspension in the form of an eye drop to treat ocular pain and inflammation following cataract surgery. Its primary objective is to assess the safety of DEXTENZA compared to the control (prednisolone acetate) in children under the age of 6 years who are undergoing cataract surgery.
Raymond Areaux
Phase III
NCT04539548
STUDY00010045
Cataract
Dextenza, dexamethasone ophthalmic insert
A Phase I, Multi-Center, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmakokinetics of CSL889 in Adult Patients with Stable Sickle Cell Disease
This study is being done to measure levels of CSL889 in the blood and see how well it is tolerated. The study will also look for changes in several blood tests related to sickle cell disease to see how the study drug might affect these measures.
Alexander Boucher
All
18 Years to 60 Years old
Phase 1
NCT04285827
STUDY00012191
Inclusion Criteria:
• Diagnosis of SCD as documented in the subject's medical record
• Aged 18 to 60 years, inclusive
• Stable SCD for at least 30 days before Day 1. Stable SCD is defined as the subject being at his or her medical baseline, with no evidence of worsening of disease over the last 30 days (including VOC, recent major surgery, hospitalization, serious infection, significant bleeding, cerebrovascular accident, seizures, or IV opioids)(Part A)
• Uncomplicated VOC requiring parenteral opioid treatment and admission to hospital for management. Uncomplicated VOC is defined as sickle cell pain without the following associated clinical features (Part B):
• Fever (> 38.5 °C)
• Hypotension (< 90/60 mmHg)
• Hypoxia (< 90% oxygen saturation on room air, or requiring oxygen therapy to maintain oxygen saturation above 90%)
• New neurological signs and / or symptoms clinically suggestive of stroke or transient ischemic attack
• Signs and / or symptoms of Acute Chest Syndrome, accompanied by any new pulmonary infiltrate on chest radiography (chest X-ray to be performed if clinically indicated and according to local clinical guidelines)
• Subject is either not taking one of the study permitted SCD therapies (hydroxyurea, L-glutamine, L-glutaminecrizanlizumab, and/or voxelotor) or subject has been taking one or more of those for at least 30 days before Day 1 and is on a stable, well tolerated regimen that is planned to continue without change throughout the study
Exclusion Criteria:
• History of primary hemorrhagic stroke
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
• Weight >110 kg (242 lbs)
• Surgery within 30 days before Day 1 or any preplanned surgeries during the study (minor surgeries may be permitted under local anesthesia before screening, with permission of the medical monitor)
• Female subjects who are pregnant or breastfeeding
• Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of CSL889.
• Treatment with any other drug / biologic that is newly approved for SCD during the conduct of this study within 90 days before Day 1. Exceptions: crizanlizumab [Adakveo®] and voxelotor [Oxbryta®] ] are permitted (where prescribed).
• Treatment with another investigational product within 30 days or within 5 half-lives of the product (whichever is greater) before Day 1
• Vaccination within 30 days before Day 1, or planned vaccination during the study
• Body-mass index < 16 kg/m2 or weight < 50 kg (110 lbs)
• History of anaphylactic-type reactions, transfusion related reaction, asthma, or autoimmune disease
Biological: CSL889
Sickle Cell Disease
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome - RECONNECT
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of CBD administered as ZYN002, a transdermal gel, for the treatment of children and adolescent patients with FXS. Qualified male and female patients with FXS will enter a two-week single-blind placebo lead-in period. Following the placebo lead-in, patients meeting randomization criteria will receive double-blind treatment for 16 weeks. The study will be comprised of a Screening visit and a combination of seven onsite (face-to-face) and virtual study visits. Approximately 204 male and female patients, ages 3 to < 18 years, will be randomized 1:1 to either trial drug or placebo. Randomization will be stratified by gender (male, female), methylation status (complete, partial), and by weight (≤50 kg, >50 kg).
Amy Esler
Phase III
NCT03802799
STUDY00014264
Fragile X Syndrome
A Phase 2, multicenter, open-label, non-randomized, proof-of-concept study evaluating the efficacy, safety, and tolerability of BIVV020 in adults with chronic inflammatory demyelinating polyneuropathy (CIDP)
The purpose of the study is to see if the drug (BIVV020) works to improve symptoms in three populations of adults who have chronic inflammatory demyelinating polyneuropathy (CIDP): • Participants currently on the standard of care (SOC) treatment. • Participants treated previously with the SOC but with no meaningful improvement. • Participants that have not been treated with the SOC. Additional purposes of the study are to find out how safe and tolerable the drug is.
Jeff Allen
18 Years and over
Phase II
NCT04658472
STUDY00014727
Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Rare Diseases
CIDP, Clinics and Surgery Center (CSC)
Open-Label Study to Evaluate the Efficacy and Safety of SCY-078 in Patients with Fungal Diseases that are Refractory to or Intolerant of Standard Antifungal Treatment (FURI) (FURI)
The purpose of this study is to see how well the experimental drug, SCY-078, works at treating people with fungal diseases that are resistant to, or unable to be treated due to bad side effects of, the Standard Antifungal Treatment that is currently used by doctors. This study will compare the effects of SCY-078 to Standard Antifungal Treatment.
Jo-Anne Young, MD
All
18 Years and over
Phase 3
NCT03059992
STUDY00000611
Key
• Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment
• Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube
• Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures.
• Be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject's personal health information. (e.g., in the U.S. HIPAA Authorization form).
• Be able to understand and follow all study-related procedures including study drug administration.
• Agree to use a medically acceptable method of contraception while receiving protocol-assigned product. Key
• An invasive fungal disease with CNS involvement.
• Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection).
• Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support.
• A life expectancy < 30 days.
• Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 5 x ULN.
• Subject is pregnant or lactating.
• Subject has used an investigational drug within 30 days prior to the baseline visit.
Inclusion Criteria:
• Must have a documented eligible invasive and/or severe fungal disease that is refractory or intolerant to Standard-of-Care treatment
• Be able to tolerate medication orally or through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube
• Be able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures.
• Be able to understand and sign a consent or authorization form which shall permit the use, disclosure and transfer of the subject's personal health information. (e.g., in the U.S. HIPAA Authorization form).
• Be able to understand and follow all study-related procedures including study drug administration.
• Agree to use a medically acceptable method of contraception while receiving protocol-assigned product. Key
Exclusion Criteria:
• An invasive fungal disease with CNS involvement.
• Subject has an inappropriately controlled fungal disease source (e.g., persistent catheters that cannot be removed and are likely the source of infection).
• Subject is hemodynamically unstable, requiring vasopressor medication for blood pressure support.
• A life expectancy < 30 days.
• Subject with abnormal liver test parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN), and/or total bilirubin > 5 x ULN.
• Subject is pregnant or lactating.
• Subject has used an investigational drug within 30 days prior to the baseline visit.
Drug: Ibrexafungerp
Invasive Candidiasis, Mucocutaneous Candidiasis, Coccidioidomycosis, Histoplasmosis, Blastomycosis, Chronic Pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis, Invasive Pulmonary Aspergillosis, Recurrent Vulvovaginal Candidiasis, Other Emerging Fungi
Clinics and Surgery Center (CSC)
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
NCT02981628
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. 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 are eligible for enrollment on Cohort 2 (dose levels 1 and -1) if asparaginase Erwinia 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
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration and Biopsy, Drug: Cyclophosphamide, Drug: Cytarabine, Procedure: Diagnostic Imaging, Biological: Inotuzumab Ozogamicin, Drug: Leucovorin Calcium, Procedure: Lumbar Puncture, Drug: Methotrexate, Drug: Pegaspargase, Drug: Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome - RECONNECT (RECONNECT)
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of CBD administered as ZYN002, a transdermal gel, for the treatment of children and adolescent patients with FXS. Qualified male and female patients with FXS will enter a two-week single-blind placebo lead-in period. Following the placebo lead-in, patients meeting randomization criteria will receive double-blind treatment for 16 weeks. The study will be comprised of a Screening visit and a combination of seven onsite (face-to-face) and virtual study visits. Approximately 204 male and female patients, ages 3 to < 18 years, will be randomized 1:1 to either trial drug or placebo. Randomization will be stratified by gender (male, female), methylation status (complete, partial), and by weight (≤50 kg, >50 kg).
Amy Esler
All
3 Years to 17 Years old
Phase 3
NCT04977986
STUDY00014264
Inclusion Criteria:
• Male or female children and adolescents aged 3 to < 18 years, at the time of Screening.
• Judged by the Investigator to be in generally good health at Screening based upon the results of medical history, physical exam, 12-lead ECG and clinical laboratory test results. -Laboratory results outside the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
• Participants must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
• Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two anti-seizure medications (ASMs) for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving ASMs.
• Patients taking psychoactive medication(s) should be on a stable regimen of not more than three such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study. Psychoactive medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
• If patients are receiving non-pharmacological, behavioral and/or dietary interventions, they must be stable and have been doing so for three months prior to screening.
• Patients have a body mass index between 12-30 kg/m2 (inclusive).
• Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
• Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
• Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures, and in the Investigator's opinion, are reliable and willing and able to comply with all protocol requirements and procedures.
Exclusion Criteria:
• Females who are pregnant, nursing or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined below for the duration of therapy and for three months after the last dose of study medication. Standard acceptable methods of contraception include abstinence (defined as refraining from heterosexual intercourse from screening to three months after the last dose of study medication) or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
• Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin levels greater than or equal to 2 times the upper limit of normal or alkaline phosphatase levels greater than or equal to 3 times the upper limit of normal.
• Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
• Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines (except midazolam or comparable administered for blood draws and ECG collection), and opiates.
• Patient is using the following AEDs (medications for the treatment of seizures and/ or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin.
• Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4 including but not limited to the following medications: midazolam (except single doses administered for the purposes of obtaining blood samples and ECG's), oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, St. John's Wort, and grapefruit Juice/products.
• Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECGs) at screening or throughout the study.
• Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
• Patient has acute or progressive neurological disease, psychosis, schizophrenia or any other psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the study objectives or ability to adhere to protocol requirements.
• Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.
• Patient has known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or other serious cardiac problems.
• Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
• Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments or absorption of the trial drug.
• History of treatment for, or evidence of, drug abuse within the past year.
• Previous participation in a ZYN002 study (with the exception of patients who were screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).
• Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study.
Drug: ZYN002 - transdermal gel, Drug: Placebo
Fragile X Syndrome
Human Genetics and Inherited Disorders, Other human genetics and inherited disorders
A Phase IIa, Double-Blind, Randomized, Intracohort Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EHP-101 in Patients with Diffuse Cutaneous Systemic Sclerosis
The primary objective of the study is to evaluate the safety and tolerability of selected doses of EHP-101 in patients with diffuse cutaneous systemic sclerosis (dcSSc) administered for up to 84 days (12 weeks).The secondary objectives of the study are to evaluate the:Treatment effect of selected doses of EHP-101 as measured by the Composite Response Index in dcSSc (CRISS) as well as all individual components of the CRISS following treatment of 84 days (12 weeks).
Jerry Molitor
All
18 Years and over
Phase 2
NCT04166552
STUDY00010677
Inclusion Criteria:
• Patients male and female ≥18 years and ≤74 years at the time of consent;
• American College of Rheumatology/ European League Against Rheumatism 2013 Criteria for SSc; dcSSc (skin thickening on upper arms, upper legs, or trunk);
• Documented SSc for up to 6 years from the first non-Raynaud's phenomenon with a total mRSS of ≥15;
• No new or increased doses of immunosuppressants medications within 3 months prior to Screening;
• Effective method of contraception for participants and their partners.
Exclusion Criteria:
• Severe or unstable Systemic Sclerosis (SSc) or SSc with end-stage organ failure;
• Patient with FVC <60%;
• History of clinically significant medical condition or concurrent medical therapies that would exclude the patient, preclude participation in the clinical trial, influence response to study product, or interfere with study assessments;
• History of gastrointestinal dysmotility requiring total parenteral nutrition or hospitalization within 6 months before Visit 1;
• Any one of the following values for laboratory tests at screening:
• Haemoglobin <9 g/dL;
• Neutrophils <1.0 x 10^9/L;
• Platelets <75 x 10^9/L;
• Estimated creatinine clearance <50 mL/min according to the Cockcroft-Gault equation;
• Serum transaminases >2.0 x upper normal limit;
• Total bilirubin ≥1.5 x upper limit of normal.
Drug: Patients will be randomized to receive EHP-101 or Placebo, Drug: Patients will be randomized to receive EHP-101 or Placebo
Arthritis & Rheumatic Diseases, Immune Diseases, Diffuse Cutaneous Systemic Sclerosis
Scleroderma, Systemic sclerosis, EHP-101 Oral Solution, dcSSc, diffuse, pathological processes, connective tissue disease, skin disease
MT2021-21 A Phase 1, Dose Escalation Study of JNJ-75229414, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against KLK2 for Metastatic Castration-Resistant Prostate Cancer
The purpose of this study is to see if a new, investigational drug called JNJ-75229414 is safe and useful for treating patients with metastatic castration-resistant prostate cancer. JNJ-75229414 is a Chimeric Antigen Receptor T Cell (CAR-T) cell therapy.
Emmanuel Antonarakis
Male
18 Years and over
Phase 1
NCT05022849
STUDY00013864
Inclusion Criteria:
• Histology: Metastatic CRPC (mCRPC) with histologic confirmation of adenocarcinoma. Metastatic CRPC with neuroendocrine features or mixed histology is excluded
• Prior Therapy: Prior treatment with at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or at least 1 prior chemotherapy (example, docetaxel)
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or detectable prostate-specific antigen (PSA) levels based on local laboratory results
• Fertile participants must use a condom with spermicide during any sexual contact with a woman of childbearing potential, including pregnant women, from the time of signing the ICF until 1 year after receiving a JNJ-75229414 infusion. Vasectomized participants must agree to use a condom to protect any sexual partner from exposure to semen for 1 year after receiving the last dose of study drug. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
Exclusion Criteria:
• Prior Grade 4 Cytokine release syndrome (CRS) or Grade 3 or Grade 4 neurotoxicity related to any T cell redirection (Bispecific cluster of differentiation [CD 3])
• Prior Kallikrein 2 (KLK2)-targeted therapy
• Prior chimeric antigen receptor T cell (CAR-T) therapy
• Receiving systemic treatment less than or equal to (<=) 6 months prior to signing informed consent) for any invasive malignancy other than prostate cancer unless approved by the sponsor. Bisphosphonates initiated greater than or equal to (>=) 6 weeks prior signing informed consent are allowed
• Less than 2 weeks between last administration anti-androgen agents (example, abiraterone or enzalutamide), poly adenosine diphosphate-ribose polymerase (PARP) inhibitors (example, olaparib) or radiotherapy, and less than 3 weeks between last administration of cytotoxic chemotherapy (example, docetaxel), radionuclides (example, radium-223, lutetium-177-Prostate-specific membrane antigen [PSMA]-617) or an investigational agent, and apheresis
Drug: JNJ-75229414, Drug: Bridging Therapy
Prostatic Neoplasms
Clinics and Surgery Center (CSC)
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Reducing Supraphysiologic Glucocorticoid Use in Adult Subjects with Classic Congenital Adrenal Hyperplasia
SPR001-204 will be a randomized, double-blind, placebo-controlled study that will evaluate the potential of tildacerfont to reduce GC burden in adult subjects with classic CAH who have lower limit of detection (LLD) ≤ A4 ≤ 1.5x upper limit of normal (ULN) and are on supraphysiologic doses of GC therapy. SPR001-204 will be the first study of tildacerfont to evaluate GC dose reduction. In addition, Study SPR001-204 will characterize clinical outcomes after up to 52 weeks of treatment with tildacerfont.
Kyriakie Sarafoglou
18 Years and over
Phase II
NCT04544410
STUDY00011764
Congenital Adrenal Hyperplasia, Diabetes & Endocrine
Adrenal Disorder, CAH, Congenital Adrenal Hyperplasia, congenital adrenal hyperplasia
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
NCT04851119
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) =<
• 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
Procedure: Dual X-ray Absorptiometry, Drug: Tegavivint, Procedure: 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
MT2020-23: A Phase I, Open-Label, Multicenter Study of FT538 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination with Monoclonal Antibodies in Relapsed/Refractory Multiple Myeloma
This is a Phase I, open-label, multicenter study to evaluate the safety, pharmacokinetics, and anti-tumor activity of FT538 in subjects with relapsed or refractory (r/r) AML and r/r MM. Subjects will be enrolled in two stages: a dose-escalation stage and a dose-expansion stage.
Mark Juckett
All
18 Years and over
Phase 1
NCT04614636
STUDY00010225
Inclusion Criteria:
• Diagnosis of one of the following by treatment regimen: Regimen A (FT538 monotherapy in r/r AML)
• Primary refractory AML, or
• Relapsed AML, defined as not in CR after one or more re-induction attempts; if >60 years of age, prior re-induction therapy is not required Regimens B or C (FT538 + mAb in r/r MM)
• Regimen B only: MM that has relapsed or progressed after at least two lines of therapies, including a proteasome inhibitor and an immunomodulatory drug
• Regimen C only: MM that has relapsed or progressed after proteasome inhibitor therapy, and immunomodulatory therapy
• Regimen B and Regimen C: Measurable disease as defined in the protocol
• Capable of giving signed informed consent
• Age ≥18 years old
• Agreement to comply with study procedures as described in the Schedule of Activities
• Contraceptive use as described in the protocol
Exclusion Criteria:
• Females who are pregnant or breastfeeding
• ECOG Performance Status ≥ 2
• Evidence of insufficient hematologic function as defined in the protocol
• Evidence of insufficient organ function defined as defined by the protocol
• Clinically significant cardiovascular disease as defined by the protocol
• Known active central nervous system (CNS) involvement by malignancy
• Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
• Currently receiving or likely to require systemic immunosuppressive therapy for any reason during the treatment period
• Clinically significant infections including HIV, HBV and HCV
• Live vaccine <6 weeks prior to start of lympho-conditioning
• Receipt of an allograft organ transplant
• Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy
• Known allergy to albumin (human) or DMSO
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject
• Any medical condition or clinical laboratory abnormality that per investigator or Medical Monitor judgement precludes safe participation in and completion of the study, or which could affect compliance with protocol conduct or interpretation of results Exclusion Criteria Specific to Regimen A (r/r AML)
• Diagnosis of promyelocytic leukemia with t(15;17) translocation
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1 Exclusion Criteria Specific to Regimens B and C (r/r MM)
• Plasma cell leukemia defined as a plasma cell count >2000/mm3
• Leptomeningeal involvement of MM
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the first dose of mAb
• Allergy or hypersensitivity to antibodies or antibody-related proteins
Drug: FT538, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Daratumumab, Drug: Elotuzumab
Acute Myeloid Leukemia, AML, Adult, Multiple Myeloma, Myeloma
Acute Myeloid Leukemia, AML, Multiple Myeloma, daratumumab, elotuzumab, NK cell, cellular therapy, allogeneic cell therapy, allogeneic cellular therapy, CD38, Anti-CD38, Clinics and Surgery Center (CSC)
A Multicenter, 6-Month, Randomized, Open-Label, Active Control, Parallel Arm, Phase 2b Study of Daily Oral LUM-201 in Naive-to-Treatment, Prepubertal Children with Growth Hormone Deficiency (GHD)
This research study is studying LUM-201 as a possible treatment for Growth Hormone Deficiency (GHD) in pre-pubertal (before puberty) children. Lumos Pharma is sponsoring this research study. Your child is being asked to be in this study because she or he has been diagnosed to have growth hormone deficiency; and your child’s study doctor thinks that your child might be a good candidate for this study. Growth hormone deficiency can result in growth failure. One of the most visible signs of growth failure is a height that is much shorter than most other children of the same age. This is called short stature. However, some children can have growth failure even if they do not have short stature. The standard treatment for growth hormone deficiency is daily injections under the skin of recombinant human growth hormone (rhGH). This study seeks to see if oral LUM-201 at various doses may achieve similar catch-up growth compared to rhGH and provide a safe and effective oral treatment alternative to daily injections. LUM-201 is to be taken by mouth and it is thought that it can increase the body’s ability to release growth hormone.
Brad Miller, MD, PhD
Phase II
NCT04614337
STUDY00011599
Growth Hormone Deficiency
Catch-up growth, GHD, Growth hormone secretagogue, Height, LUM-201, Oral, PEM, PGHD, Predictive Enrichment Marker