Status and phase
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About
This open-label Phase 1 study will evaluate the safety, PK, and antitumor activity of modified T cells (JCAR017) administered to adult patients with relapsed or refractory B-cell NHL. The dose and schedule of JCAR017 will be evaluated and modified, as needed, for safety and antitumor activity. We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma whose disease has come back or has not responded to treatment.
Full description
This is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics (PK), and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma Grade 3B, and mantle cell lymphoma (MCL). This study will evaluate and refine the dose and schedule of JCAR017 to optimize safety and antitumor activity. A dose-confirmation group or groups will further evaluate the safety and efficacy of JCAR017 at the recommended regimen(s).
Upon successful generation of JCAR017 product, participants will receive treatment with one or more cycles of JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one or two doses of JCAR017 administered by intravenous (IV) injection.
The follow-up period for each participant is approximately 24 months after the final JCAR017 infusion. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR017 infusion.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age ≥18 years
Relapsed or refractory B-cell NHL, including
PET-positive disease by Lugano classification
Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
Adequate vascular access for leukapheresis procedure
Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.
Participants must agree to use appropriate contraception.
Exclusion criteria
Active central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study)
History of other primary malignancy not in remission for at least 2 years (The following are exempt from the 2-year limit: nonmelanoma skin cancer, definitively treated stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
Treatment with alemtuzumab within 6 months of leukapheresis or fludarabine or cladribine within 3 months of leukapheresis
Active hepatitis B, hepatitis C, or Subjects with a history of or active human immunodeficiency virus (HIV) infectionare excluded. Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy
Uncontrolled systemic fungal, bacterial, viral, or other infection
Presence of graft-vs-host disease (GVHD)
History of cardiovascular disease
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Pregnant or nursing women
Use of the following:
Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment
Progressive vascular tumor invasion, thrombosis, or embolism
Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
Primary purpose
Allocation
Interventional model
Masking
387 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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