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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Juno Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02631044
First received: December 11, 2015
Last updated: May 24, 2017
Last verified: May 2017
  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.

Condition Intervention Phase
Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Follicular Lymphoma Mantle-cell Lymphoma Primary Mediastinal B-cell Lymphoma Biological: JCAR017 single-dose schedule Biological: JCAR017 2-dose schedule Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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)

Resource links provided by NLM:


Further study details as provided by Juno Therapeutics, Inc.:

Primary Outcome Measures:
  • 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

  • Maximum concentration of JCAR017 (Cmax) in the peripheral blood and bone marrow [ Time Frame: Up to 365 days after the final JCAR017 infusion ]
    Flow cytometry and qPCR

  • 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 ]
    Flow cytometry and qPCR

  • 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 ]
    Flow cytometry and qPCR


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 274
Study Start Date: December 2015
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JCAR017 single-dose schedule
Each cycle of JCAR017 will be administered as 1 intravenous (IV) injection
Biological: JCAR017 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 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.
Experimental: JCAR017 2-dose schedule
Each cycle of JCAR017 will be administered as 2 intravenous (IV) injections
Biological: JCAR017 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. Participants who respond to treatment but who have not achieved a complete response (CR) may receive additional cycles of study treatment on the dose and schedule to which they were initially assigned.

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 will further evaluate the safety and efficacy of JCAR017 at the recommended regimen.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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: 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, and willing to undergo pre- and post-treatment biopsy if at least one tumor-involved site is deemed accessible at time of screening
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  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, completely resected 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. Pregnant or nursing women
  9. 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 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
    • GVHD 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
  10. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02631044

Contacts
Contact: Juno Therapeutics 1-866-599-JUNO (5866)

Locations
United States, Alabama
University of Alabama-Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Andres Forero, MD       aforero@uab.edu   
Contact: Tiffany Hill, RN, BSN    205-996-8023    tiffanydhill@uabmc.edu   
Principal Investigator: Andres Forero, MD         
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Adam Norris       anorris@coh.org   
Principal Investigator: Tanya Siddiqi, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Leo I Gordon, MD    312-695-4546    l-gordon@northwestern.edu   
Principal Investigator: Leo I Gordon, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeremy Abramson, MD    617-724-4000    jabramson@mgh.harvard.edu   
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mary Paty Bryant       mbryant3@bidmc.harvard.edu   
Principal Investigator: Jon Arnason, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 10065
Contact: Susan Blumel, RN    402-559-9183      
Contact: Matthew Lunning, DO    402-559-5520      
Principal Investigator: Matthew Lunning, DO         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lia Palomba, MD    212-639-5317      
Principal Investigator: Lia Palomba, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Michael Wang, MD    713-792-2860    miwang@mdanderson.org   
Contact: Maria Badillo, MSN, RN    713-745-2714    mrbadill@mdanderson.org   
Principal Investigator: Michael Wang, MD         
United States, Washington
Fred Hutchinson/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Immunotherapy Trials Intake , SCCA       immunotherapy@seattlecca.org   
Principal Investigator: David G Maloney, MD, PhD         
Sponsors and Collaborators
Juno Therapeutics, Inc.
Investigators
Study Director: Tina Albertson, MD, PhD Juno Therapeutics, Inc.
Study Director: Jacob Garcia, MD Juno Therapeutics, Inc.
  More Information

Responsible Party: Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02631044     History of Changes
Other Study ID Numbers: 017001
Study First Received: December 11, 2015
Last Updated: May 24, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Juno Therapeutics, Inc.:
JCAR017
chimeric antigen receptor
non-Hodgkin lymphoma
CAR
CAR T cells
autologous T cell therapy
cell therapy
NHL

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on June 23, 2017