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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02631044
Recruitment Status : Recruiting
First Posted : December 15, 2015
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, a Subsidiary of Celgene

Tracking Information
First Submitted Date  ICMJE December 11, 2015
First Posted Date  ICMJE December 15, 2015
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Treatment-related adverse events (AEs) as assessed by CTCAE v4.03 [ Time Frame: Up to 730 days after the final JCAR017 infusion ]
    Physiological parameter
  • Dose-limiting toxicities of JCAR017 [ Time Frame: 28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion ]
    Physiological parameter
  • Objective response rate (ORR) [ Time Frame: 24 months ]
    Lugano criteria
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
  • Treatment-related adverse events (AEs) as assessed by CTCAE v4.03 [ Time Frame: Up to 365 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 ]
  • Maximum concentration of JCAR017 (Cmax) in the peripheral blood and bone marrow [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
  • Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood and bone marrow [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
  • Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood and bone marrow [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Complete response (CR) rate [ Time Frame: 24 months ]
    Lugano criteria
  • Duration of response [ Time Frame: 24 months ]
    Lugano criteria
  • Progression-free survival (PFS) [ Time Frame: 24 months ]
    Lugano criteria
  • Overall survival [ Time Frame: Up to 15 years ]
    Physiological parameter
  • Health-related quality of life [ Time Frame: 24 months ]
    Questionnaire
  • Maximum concentration of JCAR017 (Cmax) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
  • Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
  • Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2015)
  • Rate of complete response (CR), rate of partial response (PR), and objective response rate (ORR) [ Time Frame: 12 months ]
  • Duration of response (DOR) [ Time Frame: 12 months ]
  • Progression-free survival (PFS) [ Time Frame: 12 months ]
  • Overall survival [ Time Frame: Up to 15 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)
Official Title  ICMJE 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)
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Follicular Lymphoma
  • Mantle-cell Lymphoma
  • Primary Mediastinal B-cell Lymphoma
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: JCAR017 1-dose schedule
    Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection
    Intervention: Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule
  • Experimental: JCAR017 2-dose schedule (no longer accruing)
    Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections
    Intervention: Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 13, 2020)
314
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2015)
70
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02631044
Other Study ID Numbers  ICMJE 017001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Juno Therapeutics, a Subsidiary of Celgene
Study Sponsor  ICMJE Juno Therapeutics, a Subsidiary of Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Tina Albertson, MD, PhD Juno Therapeutics, Inc.
Study Director: Jacob Garcia, MD Juno Therapeutics, Inc.
PRS Account Juno Therapeutics, a Subsidiary of Celgene
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP