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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 05/30/2020.

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

Clinicaltrials.gov identifier NCT02631044

Recruitment Status Recruiting

First Posted December 15, 2015

Last update posted May 4, 2020

Study Description

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.

  • Condition or Disease:Non-Hodgkin Lymphoma
    Diffuse Large B Cell Lymphoma
    Follicular Lymphoma
    Mantle-cell Lymphoma
    Primary Mediastinal B-cell Lymphoma
  • Intervention/Treatment: Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule
    Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule
  • Phase: Phase 1
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 Design
  • Study Type: Interventional
  • Estimated Enrollment: 314 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: 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)
  • Actual Study Start Date: January 2016
  • Estimated Primary Completion Date: December 2022
  • Estimated Study Completion Date: December 2022
Arms and interventions
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.
Outcome Measures
  • Primary Outcome Measures: 1. Treatment-related adverse events (AEs) as assessed by CTCAE v4.03 [ Time Frame: Up to 730 days after the final JCAR017 infusion ]
    Physiological parameter
  • 2. Dose-limiting toxicities of JCAR017 [ Time Frame: 28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion ]
    Physiological parameter
  • 3. Objective response rate (ORR) [ Time Frame: 24 months ]
    Lugano criteria
  • Secondary Outcome Measures: 1. Complete response (CR) rate [ Time Frame: 24 months ]
    Lugano criteria
  • 2. Duration of response [ Time Frame: 24 months ]
    Lugano criteria
  • 3. Progression-free survival (PFS) [ Time Frame: 24 months ]
    Lugano criteria
  • 4. Overall survival [ Time Frame: Up to 15 years ]
    Physiological parameter
  • 5. Health-related quality of life [ Time Frame: 24 months ]
    Questionnaire
  • 6. Maximum concentration of JCAR017 (Cmax) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
  • 7. Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
  • 8. Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    qPCR
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

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

Contacts and Locations
Contacts

Contact: Juno Therapeutics 1-866-599-JUNO (5866) medicalinformation@junotherapeutics.com

Locations
Show 14 Study Locations
Sponsors and Collaborators

Juno Therapeutics, a Subsidiary of Celgene

Investigators

Study Director: Tina Albertson, MD, PhD Juno Therapeutics, Inc.

Study Director: Jacob Garcia, MD Juno Therapeutics, Inc.

More Information
  • Responsible Party: Juno Therapeutics, a Subsidiary of Celgene
  • ClinicalTrials.gov Identifier: NCT02631044 History of Changes
  • Other Study ID Numbers: 017001
  • First Posted: December 15, 2015 Key Record Dates
  • Last Update Posted: May 4, 2020
  • Last Verified: April 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Undecided
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Juno Therapeutics, a Subsidiary of Celgene: JCAR017
    chimeric antigen receptor
    non-Hodgkin lymphoma
    CAR
    cell therapy
    NHL
    CAR T cells
    autologous T cell therapy
  • Additional relevant MeSH terms: Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell
    Lymphoma, Mantle-Cell
    Lymphoma, Large B-Cell, Diffuse