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

March 26, 2024 updated by: Juno Therapeutics, a Subsidiary of Celgene

A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

387

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Local Institution - 0006
    • California
      • Duarte, California, United States, 91010-300
        • Local Institution - 0007
      • San Francisco, California, United States, 94143-0372
        • Local Institution - 0010
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Local Institution - 0020
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Local Institution - 0019
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Local Institution - 0003
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Local Institution - 0005
      • Boston, Massachusetts, United States, 02115
        • Local Institution - 0015
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • Local Institution - 0008
    • New York
      • New York, New York, United States, 10065
        • Local Institution - 0001
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Local Institution - 0021
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Local Institution - 0029
    • Texas
      • Houston, Texas, United States, 77030
        • Local Institution - 0002
    • Washington
      • Seattle, Washington, United States, 98109
        • Local Institution - 0018

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years

  2. Relapsed or refractory B-cell NHL, including

    1. 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.
    2. 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).
  3. PET-positive disease by Lugano classification
  4. 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.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
  7. Adequate vascular access for leukapheresis procedure
  8. Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.
  9. Participants must agree to use appropriate contraception.

Exclusion Criteria:

  1. Active central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study)
  2. 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)
  3. Treatment with alemtuzumab within 6 months of leukapheresis or fludarabine or cladribine within 3 months of leukapheresis
  4. 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
  5. Uncontrolled systemic fungal, bacterial, viral, or other infection
  6. Presence of graft-vs-host disease (GVHD)
  7. History of cardiovascular disease
  8. 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
  9. Pregnant or nursing women

  10. 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
  11. 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
  12. Progressive vascular tumor invasion, thrombosis, or embolism
  13. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: JCAR017 1-dose schedule
Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection
Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.
Experimental: JCAR017 2-dose schedule (no longer accruing)
Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections
Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon product availability, participants will receive study treatment consisting of lymphodepleting chemotherapy followed by two IV doses of JCAR017.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-related adverse events (AEs) as assessed by CTCAE v4.03
Time Frame: Up to 730 days after the final JCAR017 infusion
Physiological parameter
Up to 730 days after the final JCAR017 infusion
Dose-limiting toxicities of JCAR017
Time Frame: 28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion
Physiological parameter
28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion
Objective response rate (ORR)
Time Frame: 24 months
Lugano criteria
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate
Time Frame: 24 months
Lugano criteria
24 months
Duration of response
Time Frame: 24 months
Lugano criteria
24 months
Progression-free survival (PFS)
Time Frame: 24 months
Lugano criteria
24 months
Overall survival
Time Frame: Up to 15 years
Physiological parameter
Up to 15 years
Health-related quality of life
Time Frame: 24 months
Questionnaire
24 months
Maximum concentration of JCAR017 (Cmax) in the peripheral blood
Time Frame: Up to 365 days after the final JCAR017 infusion
qPCR
Up to 365 days after the final JCAR017 infusion
Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood
Time Frame: Up to 365 days after the final JCAR017 infusion
qPCR
Up to 365 days after the final JCAR017 infusion
Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood
Time Frame: Up to 365 days after the final JCAR017 infusion
qPCR
Up to 365 days after the final JCAR017 infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Juno Therapeutics, a Subsidiary of Celgene

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2016

Primary Completion (Estimated)

May 10, 2024

Study Completion (Estimated)

May 10, 2024

Study Registration Dates

First Submitted

December 11, 2015

First Submitted That Met QC Criteria

December 11, 2015

First Posted (Estimated)

December 15, 2015

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 017001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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