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413 Study Matches
Transdiagnostic Cognitive Biomarkers
The overall objective of this study is to determine the feasibility of identifying transdiagnostic biomarkers of cognitive function mediated by neuromodulation of the dorsolateral prefrontal cortex that are translatable across disease groups in order to more accurately phenotype clusters of cognitive dysfunction. Completing behavioral paradigms with electrophysiology and TMS is a challenging frontier. This study focuses on the feasibility of such an endeavor for those with chronic pain or depression as well as healthy controls.
David Darrow
STUDY00011759
Inclusion Criteria:
Chronic refractory pain or depression:
• chronic pain that is not controlled with oral pain medications or
• diagnosis of major depression
• Healthy participants: adults at least 18 years old
Exclusion Criteria:
Contraindication to TMS:
• Metallic hardware in close contact to the discharging coil (such as cochlear implants, deep brain stimulator, medication pumps)
• History of seizures
• Epilepsy
• Contraindications to MRI
• Inability to complete tasks associated with study
• Pregnancy
• Pediatric participants
• Adult lacking ability to consent
• Non-English speaking
• Blindness Healthy Controls:
• diagnosis of chronic pain or depression
Mental Health & Addiction, Brain & Nervous System
MRI, Depression, Pain, imaging, brain, TMS, stimulation, fMRI
Dissecting the role of acetaldehyde in oral carcinogenesis
The goal of this study is to better understand how drinking alcohol may lead to oral cancers. Acetaldehyde, a chemical formed when the body breaks down alcohol, is believed to play an important role. This study will measure acetaldehyde and DNA damage levels in the mouth of participants after a low dose of alcohol. The levels will be compared between three groups, all having different degrees of risk for developing oral cancer, in order to identify DNA damage that might be crucial to cancer formation.
Silvia Balbo
STUDY00012972
Inclusion Criteria:
• 21 to 45 years of age alcohol drinker
• Experiences flushing (reddening or warming of face) when you drink OR have Fanconi Anemia
• 18 to 45 years of age non-drinkers
Exclusion Criteria:
• Tobacco or nicotine users
Prevention & Wellness
Alcohol, Fanconi Anemia, drinking
MT2021-25: Phase I/II Multicenter study evaluating the Safety and Efficacy of Allogeneic GDA-201 Natural Killer cells in patients with relapsed/refractory B-Cell Non-Hodgkin Lymphoma
This study is designed to assess the safety of GDA-201 + rituximab, as well as the maximum tolerated dose in patients with B cell lymphomas in phase I; in phase II, it will assess safety and efficacy of GDA-201 in cohorts of patients with follicular lymphoma, high grade B cell lymphoma (including diffuse large B-cell), high grade B cell lymphoma not otherwise specified, and primary mediastinal B cell lymphoma.
Veronika Bachanova, MD
STUDY00015044
Inclusion Criteria:
Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows:
Received at least 2 prior lines of therapy
Transplant ineligible patients allowed assuming they meet criterion a.
Patients who received prior chimeric antigen receptor modified T-cells (CAR-T) cell therapy or are considered ineligible for CAR-T therapy per the investigator's discretion
FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL
Patients must be at least 18 years of age
Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.
Exclusion Criteria:
CNS lymphoma
Time between previous treatment and first dose of study treatment (rituximab):
Allogeneic HSCT < 6 months prior to study treatment
Autologous HSCT < 3 months prior to study treatment
CAR-T < 2 months prior to study treatment Clinics and Surgery Center (CSC)
PRE-I-SPY TRIAL - PRE-Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis: A Phase I/Ib platform trial (I-SPY)
This study is intended to find the safest dose of a new combination of drugs (ALX148 and T-DXd) and to start to determine how effective it is at treating advanced or metastatic breast cancer. This study is an addition to the ongoing ISPY study program.
David Potter
STUDY00018283
Inclusion Criteria:
• have HER2+ breast cancer
• cancer has spread to other organs or returned within 6 months after first treatment
Exclusion Criteria:
• active heart or liver disease
• cancer has spread to the brain and is causing current symptoms
Cancer, Women's Health
Clinics and Surgery Center (CSC), Breast Cancer, Breast Cancer, HER2+ breast cancer, ISPY
A RANDOMIZED PHASE III TRIAL OF OLANZAPINE VERSUS MEGESTROL ACETATE FOR CANCER-ASSOCIATED ANOREXIA (ALLIANCE A222004)
To determine whether olanzapine leads to greater appetite improvement from baseline in cancer patients suffering from anorexia compared to megestrol acetate using the 0-10 numerical rating scale (NRS).
Arjun Gupta
STUDY00014956
Inclusion Criteria:
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite?." question that requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
Exclusion Criteria:
• Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Patients who cannot swallow oral formulations of the agents
Cancer
Clinics and Surgery Center (CSC)
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
STUDY00014264
Inclusion Criteria:
Male or female children and adolescents aged 3 to < 23 years, at the time of Screening.
Patient resides with caregiver who will continue to provide consistent care throughout the study.
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.
Patient has transitioned to independent living or living in a residential facility such as a university setting or congregate care.
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.Strength and Muscle Related Outcomes for Nutrition and Lung Function in CF (STRONG-CF)
This observational study will look at physical measurements, including body mass index and body composition, and compare them to bone density scans. This study includes measurements of arm circumference, hand-grip strength, distance walked in 6 minutes, and lung function. The results of this study will provide information about the nutrition and body composition of people living with CF. This study will also help researchers understand better what contributes to malnutrition in some adults with advanced lung disease. This information will provide a baseline - or starting point - for future studies. This study may require blood draws, lung function tests, nutritional assessments, and/or other measurements.
Joanne Billings
STUDY00018144
Inclusion Criteria:
• diagnosed with Cystic Fibrosis
• clinically stable with no significant changes in health status within the 14 days prior to the first study visit
Exclusion Criteria:
• no prior solid organ transplantation
• no initiation of an investigation drug within 28 days before
• no initiation of new chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, Cayston, CFTR modulator) within 28 days
• no acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 14 days
Respiratory System, Rare Diseases, Rare Diseases
cystic fibrosis
MT2021-36: A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in combination with Azacitidine after allogeneic Stem Cell Transplantation in Subjects with Acute Myeloid Leukemia (AML) (VIALE-T) (VIALE-T)
Part 1 Primary: To determine the recommended Phase 3 dose of venetoclax in combination with azacitidine in AML subjects when given as maintenance therapy following allogeneic SCT. Part 2 primary: 1. To determine the efficacy of venetoclax in combination with azacitidine to improve RFS in AML subjects compared to BSC when given as maintenance therapy following allogeneic SCT
Mark Juckett
STUDY00014681
Inclusion Criteria:
Participants must be at least 18 years old for Part 1 and, at least 12 years old for Part 2.
Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell transplantation or have received allogeneic stem cell transplantation within the past 60 days.
Blast percentage in bone marrow before transplant must be < 10%.
Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must be < 5% after transplant.
Participant meet adequate renal, hepatic and hematologic criteria as described in the protocol.
Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score > 50 and participants between 12 to 16 years old must have a Lansky Play Performance Scale score > 40.
Exclusion Criteria:
History of disease progression during prior treatment with venetoclax.
History of any other malignancy within 2 years prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; Myelodysplastic Syndrome, Myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation).
Participant has known infection with HIV or history of being positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Presence of clinical or laboratory symptoms/signs of extramedullary myeloid malignancy. Clinics and Surgery Center (CSC)
The TrialNet Natural History Study of the Development of Type 1 Diabetes
Antoinette Moran
0305M47349
Inclusion Criteria:
Individuals 2.5 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
Individuals 2.5-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
Individuals 2.5-45 years old without a type 1 diabetes proband, who are known to have 1 or more islet antibody are eligible for screening if needed to determine eligibility for a clinical trial to delay or prevent disease progression.
Exclusion Criteria:
To be eligible a person must not:
Have diabetes already
Have a previous history of being treated with insulin or oral diabetes medications.
Currently be using systemic immunosuppressive agents (topical and inhaled agents are acceptable)
Have any known serious diseasesPEPN22P1: Pharmacokinetic Study of VinCRIStine in Infants Dosed According to BSA-Banded Infant Dosing Tables and Older Children Dosed by Traditional BSA Methods
This early phase I trial compares a new method for dosing vincristine in infants and young children to the standard dosing method based on body size in older children. Chemotherapy drugs, such as vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The same dose of a drug cannot be given to all children because they vary a lot in size from infancy to adolescence. The dose of most anticancer drugs is based on a measure of body size called the body surface area (BSA). BSA is calculated from a patient's weight and height. However, infants and young children have more severe side effects if the BSA is used to calculate their dose, so adjustments have to be made to safely give anticancer drugs to the youngest patients. A new method for dosing anticancer drugs in infants and young children has been developed that uses body size to determine the dose. Collecting blood samples over time may help researchers understand how the new vincristine dosing method affects drug levels in the blood over time in infants and young children compared to older children.
Emily Greengard
STUDY00017658
Inclusion Criteria:
Patients must be =< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:
0 to 6 months
6 months and 1 day to 12 months
12 months and 1 day to 36 months
36 months and 1 day to 12 years
Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine at the 1.5 mg/m^2 dose level
Any disease status
Patients must have a Lansky performance status of 50 or higher
Patients must be receiving a treatment regimen that includes 1.5 mg/m^2 vinCRIStine (maximum dose 2 mg)
Patients with a BSA < 0.6 m^2 must be dosed according to the Children's Oncology Group (COG) BSA-banded infant dosing table for the 1.5mg/m2 dose level for vinCRIStine
Note: Patients can be studied after any dose of vinCRIStine
Patients who are NOT enrolled on a COG clinical trial and who have a BSA < 0.6 m^2 and who are being dosed according to another infant dosing method (e.g., the 30-Rule) can receive a dose of vincristine from the infant dosing table for the pharmacokinetic study. These patients will NOT be part of the Dose Modification Assessment
Patients with a seizure disorder may be enrolled if on allowable anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
Nervous system toxicities (Common Terminology Criteria for Adverse Events [CTCAE]) version (v)5 resulting from prior therapy must be grade =< 2
Central venous access device in place (e.g., percutaneous indwelling central catheter [PICC], port, Broviac) that can be used for pharmacokinetic (PK) sampling
VinCRIStine may be given as an outpatient, as long as all sample time points can be collected, which will require return for hour 24 sampling
Exclusion Criteria:
Azoles antifungals and macrolide antibiotics: Patients who are currently receiving an azole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin, or telithromycin) are not eligible
CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances that are considered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible. Moderate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 days prior to enrollment to the end of the study. Note: dexamethasone for central nervous system (CNS) tumors or metastases, on a stable dose, is allowed
Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
Patients with Charcot-Marie-Tooth disease
A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
Patients receiving a modified dose (< 1.5 mg/m^2) of vinCRIStine due to prior toxicity
Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the studyBupropion for the Prevention of Postpartum Smoking Relapse
Sharon Allen, PhD
STUDY00007684
Inclusion Criteria:
• age 18 to 40
• lifetime history of smoking at least 100 cigarettes, quit smoking during current pregnancy
• uncomplicated delivery, at least 37 weeks gestation
• home within 10 days of delivery
• don't want to start smoking again
Exclusion Criteria:
• currently use other forms of tobacco or nicotine (e-cigs, chew, snuff, etc.)
• currently use cessation aids
• currently use illicit drugs or alcohol dependence
• taking an antidepressant
• family history of seizures or seizure disorder
Mental Health & Addiction, Women's Health
postpartum, smoking, smoking cessation
ITCC-101/APAL2020D - A randomized phase 3 trial of fludarabine/cytarabine/gemtuzumab ozogamicin with or without venetoclax in children with relapsed AML (A subtrial of the PedAL/EuPAL relapsed acute leukemia master protocol)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin [GO]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Peter Gordon
STUDY00016460
Inclusion Criteria
Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
Participants must have one of the following:
Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
Participants 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 start of protocol treatment:
Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
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 before start of protocol treatment.
Radiation therapy (RT) (before start of protocol treatment):
≥ 14 days have elapsed for local palliative RT (small port);
≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
Stem Cell Infusions (before start of protocol treatment):
≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
No evidence of active graft versus host disease (GVHD).
Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
Participants with prior exposure to venetoclax are eligible in this trial
Adequate organ function:
Adequate Renal Function defined as:
Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
Normal serum creatinine based on age/sex
Adequate Liver Function defined as:
Direct bilirubin < 1.5 x upper limit of normal (ULN), and
Alkaline phosphatase ≤ 2.5 x ULN, and
Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
Cardiac performance: Minimum cardiac function defined as:
No history of congestive heart failure in need of medical treatment
No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
No signs of congestive heart failure at presentation of relapse.
Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation.
Exclusion Criteria
Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
Participants with Down syndrome.
Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
Participants with isolated CNS3 disease or symptomatic CNS3 disease.
Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
Participants with known prior allergy to any of the medications used in protocol therapy.
Participants with documented active, uncontrolled infection at the time of study entry.
No known human immunodeficiency virus (HIV) infection.
Post menarchal female participants with positive pregnancy test.
Concomitant Medications
Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
Pregnancy or Breast-Feeding:
Participants who are pregnant or breast-feeding.
Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy.
Additional criteria to receive a gemtuzumab ozogamicin infusion:
Gemtuzumab ozogamicin should not be given:
to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
to participants with history of VOD/SOS grade 3
to participants with CD33 negative leukemic blasts (determined at local lab)
Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
A Phase 2, Randomized, Open-Label Study of Two Dose Levels of Vobramitamab Duocarmazine in Participants with Metastatic Castration-Resistant Prostate Cancer (TAMARACK) (Tamarack)
To evaluate the efficacy of MGC018 versus control as measured by rPFS by BICR using PCWG3 criteria.
Emmanuel Antonarakis
STUDY00017672
Inclusion Criteria:
• adenocarcinoma of the prostate
• received abiraterone, enzalutamide, or apalutamide to treat mCRPC
• may have had one taxane regime
• disease progression by PSA or imaging
Exclusion Criteria:
• received more than 1 prior taxane-containing regimen
• received more than 3 total prior therapies for mCRPC
• study staff will review medical and mental health history and lab values
Cancer
Clinics and Surgery Center (CSC), mCRPC, metastatic castration-resistant prostate cancer, Prostate Cancer
Phase 1/2 Study to Evaluate Palbociclib (IBRANCE?) in Combination With Irinotecan and Temozolomide or in Combination with Topotecan and Cyclophosphamide in Pediatric Patients With Recurrent or Refractory Solid Tumors Protocol No.: ADVL1921/A5481092
This is a Phase 1/2 multicenter, open-label study to evaluate palbociclib in combination with either irinotecan (IRN) and temozolomide (TMZ) or topotecan (TOPO) and cyclophosphamide (CTX) chemotherapy in children, adolescents and young adults with recurrent or refractory solid tumors. The study consists of a non- randomized Phase 1 portion for recurrent or refractory solid tumors followed by potential non- randomized tumor specific cohort(s) and a randomized, Phase 2 portion for recurrent or refractory EWS.
Emily Greengard
STUDY00007068
Inclusion:
Histologically confirmed relapsed or refractory solid tumor as follows:
For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
Age ≥2 and <21 years at the time of study entry.
Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
Adequate bone marrow function.
Absolute neutrophil count ≥1000/mm3;
Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
Hemoglobin ≥8.5 g/dL (transfusion allowed).
Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
Adequate liver function, including:
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
Exclusion:
Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
Prior irradiation to >50% of the bone marrow (see Appendix 9).
Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
Hereditary bone marrow failure disorder.
QTc >470 msec.
History of clinically significant or uncontrolled cardiac disease, including:
History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
Diagnosed or suspected congenital or acquired prolonged QT syndrome;
Need for medications known to prolong the QT interval;
Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
Left ventricular ejection fraction <50% or shortening fraction <28%.
Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
COG APEC14B1 The Project: Every Child Protocol: A Registry, Eligibility Screening, Biology and Outcome Study Additional Title: EVERYCHILD (APEC14B1) PCR - COG Foundation
This research trial studies the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.
Emily Greengard
1603M85344
Inclusion Criteria:
Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of two "2" (carcinoma in situ) or three "3" (malignant)
All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
The following other benign/borderline conditions:
Mesoblastic nephroma
Teratomas (mature and immature types)
Myeloproliferative diseases including transient myeloproliferative disease
Langerhans cell histiocytosis
Lymphoproliferative diseases
Desmoid tumors
Gonadal stromal cell tumors
Subjects must be =< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network [NCTN]) therapeutic study, for which there is a higher upper age limit
All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1A Randomized Phase II Study Comparing Sequential High dose Testosterone and Enzalutamide to Enzalutamide alone in Asymptomatic Men with Castration Resistant Metastatic Prostate Cancer
Emmanuel Antonarakis
STUDY00017208
Inclusion Criteria:
• diagnosis of adenocarcinoma of the prostate
• spread (metastatic) to other organs or bone
• previous treatment required, study staff will review
• able to care for self with little help
Exclusion Criteria:
• prior chemotherapy with docetaxel or cabazitaxel for CRPC
• other severe medical conditions, study staff will review
Cancer
Clinics and Surgery Center (CSC), Castration Resistant Metastatic Prostate Cancer (CRPC), Prostate Cancer, Prostate cancer
MT2021-24: A Phase I Open Label Study to Evaluate the Safety and Tolerability of ISP-001 in Adult Patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie
To evaluate the safety and tolerability of ISP-001 in patients with MPS I. To evaluate the long-term safety and tolerability of ISP-001. Determine the pharmacodynamic effect of ISP-001 on biomarkers in plasma, urine, and bone marrow. To explore the effect of ISP-001 on systemic manifestations of disease. Determine overall activity levels and sleep related issues.
Paul Orchard
STUDY00016974
Inclusion Criteria:
Diagnosis of Mucopolysaccharidosis type I Hurler-Scheie or Scheie syndrome.
Age ≥ 18 years at time of study registration.
Creatinine clearance, calculated or measured directly, that is >60ml/min/1.73m2.
Ejection fraction ≥ 40% by echocardiogram.
Must commit to traveling to the study site for the necessary follow-up evaluations.
Must agree to stay <45-minute drive from the study site for a minimum of 5 days after cell infusion.
Exclusion Criteria:
Known familial inherited cancer syndrome. Suspected cases will be investigated, per the physicians discretion, using relevant genetic tests to determine presence of germline mutations.
History of B cell related cancer, EBV lymphoproliferative disease or autoimmune disorders.
Evidence of active graft-vs-host disease.
Underwent a previous hematopoietic stem cell transplant (HSCT).
Requirement for systemic immune suppression.
Requirement for continuous supplemental oxygen.
Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment.
In the investigator's judgement, the subject is unlikely to complete all protocol-required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
Other protocol defined inclusion/exclusion criteria may apply. Rare Diseases
myAirvo 3 (High Flow Nasal Therapy; HFNT) for COPD patients in the home - a multi-center randomized controlled trial
Parallel-group, prospective, randomized, controlled phase III trial of home High flow Nasal Therapy (HFNT) via myAirvo 3 plus usual COPD medical care vs. usual COPD medical care, for at least 1 year and up to two years in 642 GOLD Grade D, Stages III-IV patients with moderate to very severe COPD at risk for moderate and severe exacerbations with a prior history of severe exacerbation requiring hospitalization within the past 6 weeks.
Nathaniel Gaeckle
STUDY00016166
To be eligible to participate in this study, an individual must meet all the following criteria:
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 30 years or greater
FEV1/FVC of < 70% and an FEV1 of < 80% (GOLD stages II - IV, Grade E)
• Spirometry performed during the screening visit will be used to confirm GOLD stage. A prior spirometric test within the past 6 months can be substituted if available.
MRC ≥ 2 or CAT ≥ 10
Former smokers or current smokers and never-smokers are eligible for study inclusion
• Current smokers must refrain from smoking when using supplemental oxygen or the myAirvo-3 device
History of a severe COPD exacerbation requiring hospitalization in the previous six weeks
COPD in a stable state after hospitalization defined as:
Clinically stable condition and have had no parenteral therapy for 24 hours.
Inhaled bronchodilators are required less than four-hourly.
Oxygen delivery has ceased for 24 hours (unless home oxygen is indicated).
If previously able, the patient is ambulating safely and independently, and performing activities of daily living.
The patient can eat and sleep without significant episodes of dyspnea.
The patient or caregiver understands and can administer medications.
Follow-up and home care arrangements (e.g., home oxygen, homecare, Meals on Wheels, community nurse, allied health, GP, specialist) have been completed.
Willing to adhere to the daily use of the myAirvo 3 regimen for at least 8 hours each day preferably at night following being shown and using the device
Willing to record daily symptoms and pulse oximetry and heart rate on daily basis
For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation
Highly effective contraception is defined as:
A tubal ligation:
An approved hormonal contraceptive such as oral contraceptives, emergency contraception used as directed, patches, implants, injections, rings or intrauterine devices
Able to read and communicate in English
Have a home environment suitable for myAirvo 3 use.
Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration - refraining from smoking while receiving supplemental oxygen or the myAirvo-3 device
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation in this study:
Current self-reported chronic use of positive airway pressure (PAP) therapy; continuous positive airway pressure (CPAP), or non-invasive positive pressure ventilation (NPPV)
A STOPBang Questionnaire score > 5*
Pregnancy or lactation
Treatment with another investigational drug or other intervention within the previous 30 days
Life expectancy less than 12 months due to COPD or other comorbid condition.
Recent upper airway surgery (within the previous month)
Recent head or neck trauma (within the previous month)
Inability to tolerate nasal prongs
Requirement of oxygen greater than 15 L/min
subjects with a STOPBang questionnaire score of > 5 may be eligible if a recent sleep study (within the previous 3 months) shows the absence of obstructive sleep apnea or the subject has, or is at risk of OSA, but refuses to use an OSA device and all other eligibility criteria are met.MT2022-27: TRANSPIRE: Lung Injury in a Longitudinal Cohort of Pediatric HSCT Patients
Primary Purpose: To identify risk factors and mechanisms of lung injury, test novel diagnostic strategies and treatments to reduce morbidity and mortality from lung injury after transplant.
Samuel Goldfarb
STUDY00016089
Inclusion Criteria:
Subjects ≤ 24 years of age undergoing allogeneic or autologous HSCT.
Exclusion Criteria:
Subjects over 24 years of age.MT2017-45 :Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients with Hematologic Malignancies
This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. The study provides criteria for consistent treatment and management according to FDA labelling of CAR-T products and does not contain experimental components. Patients will be assigned to Arms A B and C based on age, CAR-T product and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arms A B and C separately.
Veronika Bachanova, MD
STUDY00004096
ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
Inclusion Criteria:
Age and Disease Status
Must be age 0-25 years (for Arm A Kymriah) or >18 years (Arm G Tecartus)
Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
Patients in 2nd or greater relapse of B-ALL or
Patients with persistent CNS leukemia, or
Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
Performance Status
* Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
** ALT ≤ 5 times the ULN for age (unless due to disease)
** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Other Inclusion Criteria
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
CNS 2A
CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1
ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
One of the following histologies and expression of CD19 by tumor cells:
** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
** primary mediastinal large B-cell lymphoma, or
** high grade B-cell lymphoma, or
** DLBCL arising from follicular lymphoma
Disease status:
** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
ECOG performance status 0-2
ALC >/=100/uL at screening (prior to apheresis)
Renal function defined as:
** A serum creatinine of ≤1.5 x ULN OR
** eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
Platelets ≥ 50.000/mm3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection (controlled HIV is permissible)
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe.
ARM C: Kymriah for rRelapsed or rRefractory diffuse large B cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
with relapsed or refractory (r/r) large B-cell lymphoma, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
high grade B-cell lymphoma
and DLBCL arising from follicular lymphoma.
Disease status:
after two or more lines of systemic therapy or
relapse after autologous HCT
Performance Status
ECOG performance status 0-2
ALC >/=100/uL at screening (prior to apheresis)
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m^2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
Platelets ≥ 50.000/mm3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis.
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM D: Tecartus (Brexucabtagene Autoleucel) for relapsed or refractory mantle cell lymphoma
Inclusion Criteria:
Age and Disease Status
* with relapsed or refractory (r/r) mantle cell lymphoma, including
prior anthracycline or Bendamustine containing therapy
prior Rituximab or other CD20 directed antibody (or inability to treat with CD20 MoAb)
not a candidate or relapse after autologous HCT
active disease at enrollment
Performance Status
*ECOG performance status 0-1
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM E: Breyanzi "lisocabtagene maraleucel" for relapsed or refractory large B-cell lymphoma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
with relapsed or refractory disease after two or more lines of systemic therapy, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma),
high-grade B-cell lymphoma,
primary mediastinal large B-cell lymphoma,
follicular lymphoma grade 3B
Performance Status
*ECOG performance status 0-2
Organ Function
Renal function defined as:
A serum creatinine of ≤1.5 x ULN OR
eGFR ≥ 30 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 40% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe
ARM F: Abecma "Idecabtagene Vicleucel" for relapsed or refractory multiple myeloma
Inclusion Criteria:
Age and Disease Status
Adult patients (age ≥ 18 years)
Relapsed (progression after prior partial or complete remission) or refractory multiple myeloma
Evidence of active disease (medullary or extramedullary)
Prior therapy (Failure or intolerance to) with an immunomodulatory agent, a proteasome inhibitor, and an antiCD38 monoclonal antibody
Performance Status
*ECOG performance status 0-1
Organ Function
Renal function defined as:
A serum creatinine of ≤2 x ULN OR
eGFR ≥ 50 mL/min/1.73 m2
Liver function defined as:
ALT ≤ 5 times the ULN for age (unless due to disease)
Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3 (only for NHL)
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided)
Other Inclusion Criteria:
Life expectancy ≥12 weeks
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment. See section 4.5 for definitions of child bearing potential and section 4.6 for definitions of adequate birth control.
Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
Uncontrolled active hepatitis B or hepatitis C
Active HIV infection
Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
Intolerance to the excipients of the CAR-T cell product
Any immunosuppressive medication must be stopped ≥ 2 weeks prior to apheresis (steroids must be stopped >72 hours prior to apheresis).
Patient has taken one of the prohibited concomitant medications within the timeframe Clinics and Surgery Center (CSC)
A Randomized, Comparative Effectiveness Study of Staged Complete Revascularization with Percutaneous Coronary Intervention to Treat Coronary Artery Disease vs Medical Management Alone in Patients with Symptomatic Aortic Valve Stenosis undergoing Elective Transfemoral Transcatheter Aortic Valve Replacement: The COMPLETE TAVR Study (COMPLETE TAVR)
The study will be a randomized, multicenter, open-label trial with blinded adjudication of outcomes.
Greg Helmer
STUDY00012707
Inclusion Criteria:
Men and women with severe symptomatic aortic valve stenosis defined as: [aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2] AND [Jet velocity ≥ 4.0 m/s or mean gradient ≥ 40 mmHg] AND [NYHA Functional Class ≥ 2 OR abnormal exercise test with severe SOB, abnormal blood pressure response, or arrhythmia]
AND
Coronary artery disease defined as: (at least 1 coronary artery lesion of ≥70% visual angiographic diameter stenosis in a native segment that is at least 2.5 mm in diameter that is not a CTO and is amenable to treatment with percutaneous coronary intervention (PCI))
AND
Consensus by the Multidisciplinary Heart Team that the patient is suitable for elective transfemoral transcatheter aortic valve replacement (TAVR) with a balloon expandable transcatheter heart valve AND would receive a bypass with an anastomosis distal to the coronary artery lesion(s) if they were undergoing surgical aortic valve replacement.
AND
Successful TAVR defined as the implantation of a single transcatheter aortic valve within the past 96 hours with freedom from more than minimal aortic insufficiency, stroke, or major vascular complications
Exclusion Criteria:
PCI already performed within 90 days prior to TAVR or at the same time as the index transfemoral TAVR procedure
Planned PCI of coronary artery lesion(s)
Planned surgical revascularization of coronary artery lesion(s)
Non-cardiovascular co-morbidity reducing life expectancy to < 5 years
Any factor precluding 5-year follow-up
Prior coronary artery bypass grafting surgery or surgical valve replacement
Severe mitral regurgitation (> 3+)
Severe left ventricular dysfunction (LVEF < 30%)
Low coronary takeoff (high risk for coronary obstruction)
Acute myocardial infarction within 90 days
Stroke or transient ischemic attack within 90 days
Renal insufficiency (eGFR < 30 ml/min) and/or renal replacement Rx
Hemodynamic or respiratory instability Clinics and Surgery Center (CSC)
A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients with Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum
We are looking at how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body and may stop the growth of tumor cells that need estrogen to grow. We will compare the effectiveness of the two different treatments.
Rahel Ghebre, Dr
MMCORC048
Inclusion Criteria:
• newly diagnosed, stage II-IV low-grade serous ovarian cancer fallopian tube or primary peritoneal cancers
• surgery for maximal cytoreduction completed within 8 weeks of randomization
• bilateral salpingo-oophorectomy completed
• able to take oral medications
Exclusion Criteria:
• prior neoadjuvant chemotherapy, endocrine therapy or radiotherapy for the treatment of this disease
• severe cardiac disease
Cancer
Fallopian Tube cancer, Ovarian cancer, Peritoneal cancer, Serous carcinoma
MT2020-33: Study of FT538 in Combination with Daratumumab in Acute Myeloid Leukemia
This study is designed to find the maximum tolerated dose (MTD) of FT538 when given in combination with daratumumab for the treatment of acute myeloid leukemia (AML).
Joseph Maakaron
STUDY00012524
Disease specific
Inclusion Criteria:
Acute myeloid leukemia relapsed/refractory after 2 lines of therapy; with CD38 expression
CD38 expression is defined by ≥20% of malignant cells with CD38 expression by flow cytometry on the most recent marrow biopsy (within 30 days of enrollment - archived or fresh).
Relapsed/refractory is defined as failure to achieve at least a Morphological Leukemia Free State (MLFS) or reverting from MLFS.
Lines of therapy are defined as (must have had 2 prior therapies):
One cycle of Intensive induction chemotherapy such as 7+3, 5+2, MEC, FLAG, FLAG-Ida, CLAG ± small molecule inhibitor
Four weeks of HMA-based induction ± small molecule inhibitor
Hematopoietic stem cell transplantation (HSCT) if relapse that occurs > 90 days after HSCT
Gemtuzumab Ozogamicin
LDAC + glasdegib
Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, others if available)
Other treatments could be considered after discussion with the PI
Inclusion Criteria:
Age 12 years or older at the time of consent - Please note, enrollment of minors will be begin until permission to proceed is received from the FDA. At that time, the protocol will be updated to open enrollment to minors.
Weight ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dose packaging
Karnofsky performance status of 80-100% for 16 years and older or Lansky Play Score of 80-100 for ≥12 and < 16 years of age
Evidence of adequate organ function within 14 days of starting study treatment defined as:
Estimated Glomerular Filtration Rate (estimated creatinine clearance) ≥50 mL/min/1.73m^2
Total bilirubin ≤ 5 × upper limit normal (ULN), not applicable for patients with Gilbert's syndrome
AST ≤3 × ULN and ALT ≤ 3 × ULN, not applicable if determined to be directly due to underlying malignancy
LVEF ≥ 40% by echocardiogram or MUGA
Contraceptive use by men or women
Female subjects: Women of childbearing potential (WOCBP) must use a highly effective form of contraception from the screening visit until at least 12 months after the final dose of cyclophosphamide (CY), at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
Male subjects: Males with a female partner of childbearing potential or a pregnant female partner must be sterile (biologically or surgically) or use a highly effective method of contraception from the screening visit until at least 4 months after the final dose of CY and at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.
Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.
Exclusion Criteria:
Diagnosis of acute promyelocytic leukemia (APL)
Pregnant or breastfeeding, Menstruating females of child-bearing potential must have a negative pregnancy test within 14 days of study treatment start
Known allergy to any of study drugs or their components
Clinically significant cardiovascular disease including any of the following: myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher or cardiac ejection fraction <40%
Any known condition that requires systemic immunosuppressive therapy (> 5mg prednisone daily or equivalent) during the FT538 dosing period (3 days before the 1st dose through 14 days after the last dose) excluding pre-medications - inhaled and topical steroids are permitted
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 to the first dose of daratumumab. Maintenance hydroxyurea for blast control up to the initiation of lympho-conditioning is permitted
Known active central nervous system (CNS) involvement or treated CNS disease that has not cleared. If prior disease related CNS involvement must have completed effective treatment of their CNS disease at least 2 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging
Non-malignant CNS disease such as epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
Clinically significant untreated/uncontrolled infection
Live vaccine <6 weeks prior to start of lympho-conditioning
Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR
Prior solid organ transplant
Allogeneic HSCT relapse occurring <90 days after HSCT
Active graft-versus-host-disease (GvHD) requiring systemic immunosuppression within 14 days prior to enrollment
Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to the participant. Clinics and Surgery Center (CSC)
MT2020-27: Phase I/II Trial Using E7777 to Enhance Regulatory T-Cell Depletion Prior to Tisagenlecleucel (Kymriah) Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
This purpose of this study is to identify a safe dose level for the study drug, E7777, when given with standard tisagenlecleucel therapy (also known by its brand name, Kymriah, is an immunotherapy that is made from the participants own blood cells) in participants with Diffuse Large B-Cell Lymphoma (DLBCL). Up to three dose levels of E7777 will be tested.
Veronika Bachanova, MD
STUDY00011895
Inclusion Criteria:
Diagnosis of a relapse or refractory (r/r) large B cell lymphoma, for which treatment with Kymriah is planned, including:
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
high grade B-cell lymphoma
DLBCL arising from follicular lymphoma
Considered at high risk for progression after CAR-T therapy by meeting one or more of the following factors:
refractory to last line of therapy
myc over expression >40% in any prior biopsy
≥2 sites of extranodal disease
Received two or more lines of systemic therapy
Has secured insurance coverage for Kymriah administration either in the outpatient or inpatient setting.
Age 18 years or older at the time of signing consent.
ECOG performance status of 0, 1, or 2
Adequate bone marrow reserve defined as:
Absolute neutrophil count (ANC) > 1,000/mm^3
Platelets ≥ 50,000/mm^3 (transfusion support can be provided)
Hemoglobin >8.0 mg/dl (transfusion support can be provided) Bone marrow involvement at disease assessment is an exclusion as these patients are at an increased risk of severe CRS and/or neurotoxicity
Adequate organ function at enrollment and within 14 days of planned E7777 treatment including:
renal function: eGFR ≥ 50 mL/min/1.73 m^2
liver function: ALT ≤ 3 times the upper limit of normal (ULN) for age, AST ≤ 3 times the ULN, total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN (if liver is involved by lymphoma, the exception are allowed upon approval of PI)
albumin ≥ 3.0 g/dl
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea (CTCAE v5) and pulse oxygenation SpO2 > 91% on room air. Pulmonary function tests within 28 days of enrollment: >50% corrected DLCO and FEV1
Hemodynamically stable and LVEF ≥ 50% confirmed by echocardiogram or MUGA
Life expectancy ≥12 weeks in the opinion of the enrolling investigator as documented in the medical record
Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use birth control for at least 30 days after study treatment or at least at least 4 months after the final dose of CY, whichever is longer Female participants: Two forms of birth control, one of which must be a barrier method, for example: use of intrauterine device (IUD) or oral contraceptives, plus a barrier method such as a condom, diaphragm or cervical cap Male participants: If possible to father a child (unless a successful vasectomy with confirmed azoospermia) participant and female partner, must use adequate contraception
Written voluntary consent prior to the performance of any research related tests or procedures
Exclusion Criteria:
Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Known bone marrow involvement, if history of bone marrow involvement must have a BM biopsy to rule-out current involvement
Prior allogeneic transplant
Ocular disease or complaints visual acuity impairment, color or shape distortion, or blurred vision - potential participants are required to have an ophthalmological examine as part of screening
Known CNS involvement by malignancy - if clinically suspicious, must be ruled-out by examination of cerebrospinal fluid (CSF) by flow cytometry
Uncontrolled active hepatitis B or hepatitis C
Active or inactive HIV infection
Untreated active bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to enrollment)
History of heart failure or pulmonary edema, evidence of pleural effusion or active lower extremity edema
Uncontrolled unstable angina and/or myocardial infarction within 3 months of enrollment
Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion Clinics and Surgery Center (CSC)
A Phase 1, First in Human, Dose-Escalation Study of TORL-1-23 in Participants with Advanced Cancer (TRIO049)
This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-1-23 in patients with advanced cancer.
Boris Winterhoff
STUDY00014893
Inclusion Criteria:
Advanced solid tumor
Measurable disease, per RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Adequate organ function
Exclusion Criteria:
Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements
Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-1-23
Progressive or symptomatic brain metastases
Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection
History of significant cardiac disease
History of myelodysplastic syndrome (MDS) or AML
History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded
If female, is pregnant or breastfeeding Clinics and Surgery Center (CSC)
MT2022-40: A Phase 3 Double-Blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of AB-205 plus Standard of Care versus Placebo plus Standard of Care in Adults with Lymphoma Undergoing High-Dose Therapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT) (E-CELERATE) (E-CELERATE)
To demonstrate a reduction in the incidence and severity of regimen related toxicities with AB-205 plus standard of care (SoC) versus placebo plus SoC in adults with lymphoma undergoing HDT-AHCT.
Daniel O'Leary
STUDY00016649
Inclusion Criteria:
Age ≥ 40 years old
Diagnosis of Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL)
Candidates for HDT-AHCT with one of the following conditioning regimens:
BEAM (carmustine, etoposide, cytarabine, melphalan)
BeEAM (bendamustine, etoposide, cytarabine, melphalan)
Achieved CR or PR prior to planned HDT
ECOG ≤ 2
Weight ≤ 1.6 × ideal body weight (IBW) per Devine formula
Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia
AST, ALT, and alkaline phosphatase < 3 × ULN
Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft Gault)
LVEF ≥ 45% by MUGA or resting echocardiogram
Pulmonary function (FEV1 and corrected DLCO) ≥ 45% predicted
Willingness and ability to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
Sexually active females of childbearing potential must have a negative urine pregnancy test and agree to use two accepted methods of contraception during the study and for 3 months after their last dose of study drug.
Male subjects who are sexually active and who are partners of females of childbearing potential: agreement to use two forms of contraception as in criterion 12 above and to not donate sperm during the treatment period and for at least 3 months after the last dose of study drug
Ability to provide written informed consent.
Exclusion Criteria:
History of prior HCT
Primary CNS lymphoma
Lymphoma with CNS involvement at time of relapse prior to planned HDT-AHCT
Active malignancy other than the one for which the subject is undergoing HDT AHCT. Subjects with cervical carcinoma in situ or localized basal or squamous cell carcinoma treated with definitive surgery are eligible
Subjects with a serious concomitant medical condition that could interfere with the conduct of the clinical trial, such as unstable angina, renal failure requiring hemodialysis, or active infection requiring IV antibiotics
Subjects with a known history of HIV
Subjects who have known hypersensitivity reactions to bovine (cow) proteins or documented allergy to DMSO
Subject has other conditions that in the opinion of the investigator would require reduced dose (intensity) of BEAM or BeEAM regimensA Phase 1/2, Multi-Center, Dose-Escalating Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Quizartinib Administered in Combination with Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to < 18 Years (and Young Adults Aged up to 21 Years) with FLT3-ITD Mutations (Protocol Number: AC220-A-U202/ADVL1822)
This is an open-label, multi-center, single arm, Phase 1/2 study to evaluate the safety, PK, PD, and efficacy of quizartinib administered in combination with fludarabine and cytarabine (FLA) (Re-Induction Cycles 1 and 2) chemotherapy for re-induction, with optional consolidation chemotherapy, and as a single agent continuation therapy (after optional, but strongly encouraged, HSCT per standard of care), in pediatric relapsed/refractory AML subjects aged ≥1 month old to <18 years old (and young adults up to 21 years old) with FLT3-ITD mutations.
Emily Greengard
STUDY00005937
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment into the study:
Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
In first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
Has protocol-defined adequate performance status score
Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
Has protocol-defined adequate renal, hepatic and cardiac functions
If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later
If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
Male participants must be surgically sterile or willing to use highly effective birth control during the treatment period, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later.
Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
Exclusion Criteria:
Participants who meet any of the following criteria will be disqualified from entering the study:
Has been diagnosed with isolated central nervous system relapse, acute promyelocytic leukemia (APL), juvenile myelomonocytic leukemia, French-American-British classification M3 or WHO classification of APL with translocation, or with myeloid proliferations related to Down syndrome
Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
Has known history of human immunodeficiency virus (HIV)
Has history of hypersensitivity to any of the study medications or their excipients
Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
Is otherwise considered inappropriate for the study by the InvestigatorANHL2121: Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell Histiocytosis
This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.
Lucie Turcotte
STUDY00019528
Inclusion Criteria:
180 days- < 22 years (at time of study enrollment)
Patients with multifocal progressive, relapsed, or recurrent LCH with measurable disease at study entry
Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
Tissue confirmation of relapse is recommended but not required
Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
Patients must have measurable disease, documented by radiographic imaging (LCH- specific response criteria (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary).
Patients must have progressive or refractory disease or experience relapse after at least one previous systemic chemotherapy treatment strategy
Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16 years of age
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
Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent for at least 14 days prior to planned start of tovorafenib (DAY101)
Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
Patients must have fully recovered from any prior surgery
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy with toxicities reduced to Grade 1 or less (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Steroids: < 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to study enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to study enrollment
Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
Peripheral absolute neutrophil count (ANC) >= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Platelet count >= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Patients with marrow disease must have platelet count of >= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
Hemoglobin >= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin >= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta [registered trademark]) or 7 days for short-acting growth factor
A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Age: 6 months to < 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
Age: 1 to < 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
Age: 2 to < 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
Age: 6 to < 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
Age: 10 to < 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
13 to < 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
Age: >= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
OR- a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2
OR- a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Alanine aminotransferase (ALT) =< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
Serum albumin >= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
Fractional shortening (FS) of >= 25% or ejection fraction of >= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
Central Nervous System Function Defined As:
Patients with seizure disorder may be enrolled if well controlled
Central nervous system (CNS) toxicity =< Grade 2
Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
Exclusion Criteria:
LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy
Disease scenarios as below will be excluded
Skin-limited disease
Single bone lesion
Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
Patient must not have received any prior MAPK pathway inhibitor therapy
Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
Uncontrolled systemic bacterial, viral, or fungal infection
Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
History of solid organ or hematopoietic bone marrow transplantation
Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval > 440 ms based on triplicate electrocardiogram (ECG) average
History of Grade >= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
CTCAE version (V). 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation ( > 5 x ULN)
Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants are ineligible
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Participants (male and female) who are sexually active must use two forms of an acceptable method of birth control (for men, one form must be a barrier method) from start of therapy through 180 days following last dose of tovorafenib (DAY101)A randomized phase II trial of adjuvant Pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153
The primary objective is to evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1 TPS score.
Amit Kulkarni
STUDY00010745
Inclusion Criteria:
• at least 18 years old
• diagnosis of non-small cell lung cancer (NSCLC)
• tumor size between 1 and 4 cm in size -had complete surgical resection of stage I NSCLC between 4-12 weeks ago
• able to walk and carry out basic activities of living
• women are willing to use highly effective birth control for 120 days after last dose of study drug
• certain laboratory values are required (study staff will review)
Exclusion Criteria:
• chemotherapy, radiation therapy, or immunotherapy for the treatment of this lung cancer
• active additional cancer that is progressing or has required treatment within the past 3 years
• diagnosis of immunodeficiency or receiving chronic steroid therapy
• women who are pregnant or breast feeding
• other active diseases (study staff will review)
Cancer
Clinics and Surgery Center (CSC), Lung Cancer, Lung Cancer, Non-small Cell Lung Cancer (NSCLC)
Phase II trial of androgen deprivation therapy (ADT) and pembrolizumab for advanced stage androgen receptor-positive salivary gland carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111
We are looking at the effectiveness of adding an immunotherapy drug, pembrolizumab, to usual treatment for people who have salivary gland cancer that can’t be treated with surgery or radiation. The cancer must be androgen receptor positive.
Manish Patel
STUDY00004710
Inclusion Criteria:
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
Locally advanced, recurrent, or metastatic salivary gland carcinoma that is not amenable to curative surgery or radiation
ECOG Performance Status of 0 or 1 within 28 days prior to registration.
Local, pathologic testing of androgen receptor-positive salivary gland carcinoma will be performed as standard of care. Archival tissue must be available for central confirmation of androgen receptor-positive disease and for correlative studies. AR positivity will be defined according to IHC staining of tumor tissue with at least 20% of tumor staining positive with moderate intensity (1+ or greater).
Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.
For patients who have been treated with prior therapy, patients must have documented progression of disease on their prior therapy for entry into the study.
Patients with prior chemotherapy, radiation, or surgery as part of curative intent therapy are allowed. Any number of prior lines of systemic therapy is permitted for entry into this study so long as prior therapy did not include anti-androgen therapy or immune checkpoint blockade.
If prior cancer treatment, the subject must have recovered from toxic effects of prior cancer treatment (other than alopecia) to ≤ Grade 1.
Adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
Absolute neutrophil count (ANC) ≥1500/µL
Platelets ≥100,000/µL
Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
Creatinine (Cr) OR Measured or calculated creatinine clearance (GFR can also be used in place of Cr or creatinine clearance) ≤1.5 × ULN OR
≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) o International normalized ratio (INR) OR prothrombin time (PT) & aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
A male participant must agree to use contraception during the treatment period and for at least 8 months after the last dose of study treatment and refrain from donating sperm during this period.
Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
Females of childbearing potential and males with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effect form of contraception from the time of informed consent until 8 months after treatment discontinuation.
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion Criteria:
Women of childbearing age with a positive serum pregnancy test within 72 hours prior to study registration.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
Has received prior androgen deprivation therapy including orchiectomy, gonadotropin-releasing hormone (GnRH) agonists/antagonists, androgen receptor blocker, abiraterone, or enzalutamide.
Has received prior systemic anti-cancer therapy including investigational agents within 14 days prior to registration.
Has had an allogenic tissue or solid organ transplant.
Has received prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities and require less than 10mg of prednisone (or equivalent corticosteroid) daily.
Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 14 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Has ≥Grade 3 hypersensitivity to pembrolizumab and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV).
Has a known history of active TB (Bacillus Tuberculosis).
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Clinics and Surgery Center (CSC)