Non Hodgkin Lymphoma Clinical Trial

Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)

Summary

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.

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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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years

Relapsed or refractory B-cell NHL, including

DLBCL cohort (no longer enrolling): DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology [tDLBCL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of systemic therapy or after auto-HSCT.
MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization [FISH], or PCR) with relapsed or refractory disease after at least 2 prior lines of systemic MCL therapy. Subjects must have been treated with an alkylating agent, Bruton's tyrosine kinase inhibitor (BTKi), and rituximab (or other CD20-targeted agent).
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:

Therapeutic doses of corticosteroids (defined as >20 mg/day prednisone or equivalent) within 7 days of leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, topical, and inhaled steroids are permitted.
Low dose chemotherapy (e.g., vincristine, rituximab, cyclophosphamide ≤300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥7 days prior to lymphodepleting chemotherapy.
Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) within 2 weeks of leukapheresis.
Experimental agents within 4 weeks of leukapheresis unless no response or disease progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis
Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017 administration (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolyate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti IL6, or anti-IL6R)
Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration
Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to leukapheresis.
Allo-HSCT within 90 days of leukapheresis
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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

385

Study ID:

NCT02631044

Recruitment Status:

Active, not recruiting

Sponsor:

Juno Therapeutics, a Subsidiary of Celgene

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There are 15 Locations for this study

See Locations Near You

Local Institution - 0006
Birmingham Alabama, 35294, United States
University of Alabama-Birmingham
Birmingham Alabama, 35294, United States
Local Institution - 0007
Duarte California, 91010, United States
City of Hope
Duarte California, 91010, United States
University of California San Francisco
San Francisco California, 94143, United States
Local Institution - 0020
Aurora Colorado, 80045, United States
University of Colorado
Aurora Colorado, 80045, United States
Blood Marrow Transfer Group of Georgia - Northside Hospital
Atlanta Georgia, 30342, United States
Local Institution - 0003
Chicago Illinois, 60611, United States
Northwestern University
Chicago Illinois, 60611, United States
Local Institution - 0005
Boston Massachusetts, 02114, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Local Institution - 0015
Boston Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
University of Nebraska Medical Center
Omaha Nebraska, 10065, United States
Local Institution - 0008
Omaha Nebraska, 68198, United States
Local Institution - 0001
New York New York, 10065, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Levine Cancer Institute
Charlotte North Carolina, 28204, United States
Local Institution - 0021
Charlotte North Carolina, 28204, United States
UPMC Hillman Cancer Center
Pittsburgh Pennsylvania, 15232, United States
Local Institution - 0002
Houston Texas, 77030, United States
MD Anderson Cancer Center
Houston Texas, 77030, United States
Fred Hutchinson/University of Washington Cancer Consortium
Seattle Washington, 98109, United States
Local Institution - 0018
Seattle Washington, 98109, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

385

Study ID:

NCT02631044

Recruitment Status:

Active, not recruiting

Sponsor:


Juno Therapeutics, a Subsidiary of Celgene

How clear is this clinincal trial information?

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