Clinical Trials /

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

NCT02631044

Description:

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.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 017001
  • NCT ID: NCT02631044

Conditions

  • Non-Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Follicular Lymphoma
  • Mantle-cell Lymphoma
  • Primary Mediastinal B-cell Lymphoma

Interventions

DrugSynonymsArms
JCAR017 (lisocabtagene maraleucel) single-dose scheduleJCAR017 1-dose schedule
JCAR017 (lisocabtagene maraleucel) 2-dose scheduleJCAR017 2-dose schedule

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
JCAR017 1-dose scheduleExperimentalEach cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection
  • JCAR017 (lisocabtagene maraleucel) single-dose schedule
JCAR017 2-dose scheduleExperimentalEach cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections
  • JCAR017 (lisocabtagene maraleucel) 2-dose schedule

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years

          2. Relapsed or refractory B-cell NHL, including

               1. DLBCL cohort: 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 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 1 prior line of MCL
                  therapy

          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 human immunodeficiency virus (HIV) infection

          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, ifosofamide,
                  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-related adverse events (AEs) as assessed by CTCAE v4.03
Time Frame:Up to 730 days after the final JCAR017 infusion
Safety Issue:
Description:Physiological parameter

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Juno Therapeutics, Inc.

Trial Keywords

  • JCAR017
  • chimeric antigen receptor
  • non-Hodgkin lymphoma
  • CAR
  • CAR T cells
  • autologous T cell therapy
  • cell therapy
  • NHL

Last Updated

December 19, 2019