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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 September 2016 by Juno Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02631044
First received: December 11, 2015
Last updated: September 13, 2016
Last verified: September 2016
  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: 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)

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 ]
  • 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 ]
  • Rate of complete response (CR), rate of partial response (PR), and objective response rate (ORR) [ Time Frame: 24 months ]
  • Duration of response (DOR) [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 24 months ]
  • Overall survival [ Time Frame: Up to 15 years ]

Estimated Enrollment: 144
Study Start Date: December 2015
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 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 product availability, participants will receive study treatment consisting of lymphodepleting chemotherapy followed by one IV dose 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.
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.

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

    a. DLBCL cohort: DLBCL, not otherwise specified (NOS), per WHO classification, including transformed DLBCL from indolent histology (tDLBCL), 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 one of the following:

    i. Biopsy-proven refractory disease after frontline chemo-immunotherapy

    ii. Relapsed or refractory disease after at least 2 lines of therapy or after autologous hematopoietic stem cell transplant (auto-HSCT); subjects with tDLBCL must have received at least 1 line of therapy after transformation to DLBCL.

    iii. Relapsed or refractory disease after allogeneic hematopoietic stem cell transplant (allo-HSCT)

    b. MCL cohort: Mantle-cell lymphoma with relapsed or refractory disease after at least 1 prior line of MCL therapy

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

Exclusion Criteria:

  1. Active central nervous system (CNS) involvement by malignancy
  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, 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
  9. Pregnant or nursing women
  10. Use of the following:

    1. Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, topical, and inhaled steroids are permitted.
    2. Allo-HSCT within 90 days of leukapheresis
    3. Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 administration
    4. GVHD therapies within 4 weeks of leukapheresis and JCAR017 administration
    5. Cytotoxic chemotherapeutic agents within 1 week of leukapheresis. Oral chemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
    6. Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis
    7. Experimental agents within 4 weeks of leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis
    8. Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, positron emission tomography (PET)-positive lesions to be eligible.
  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
  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

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         
Sponsors and Collaborators
Juno Therapeutics, Inc.
Investigators
Study Director: Tina Albertson, MD, PhD 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: September 13, 2016
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 March 28, 2017