Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
017001 (primary)
NCI-2016-00057
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.
Objectives
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.
Eligibility
- 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.
Treatment Sites in Georgia
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