Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed or Refractory Multiple Myeloma (EVOLVE)

Overview

This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in subjects who receive prophylactic treatment with anakinra will be evaluated in a separate Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.

SparkCures ID 940
Trial Phase Phase 1/2
Enrollment 245 Patients
Treatments
Tags
Trial Sponsors
  • Juno Therapeutics, a Subsidiary of Celgene
NCT Identifier

NCT03430011

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Key Inclusion Criteria:

  1. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory (R/R) disease. Participants must have received at least 3 prior anti-myeloma treatment regimens. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study (not applicable to Phase 2a):

    1. Autologous stem cell transplant
    2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination
    3. Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy

    Subjects who have received prior allogeneic stem cell transplant or donor lymphocyte infusion at least 100 days before enrollment with no signs of acute or chronic graft-versus-host disease (GVHD) will be considered eligible. Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible.

  2. Subjects must have measurable disease.
  3. Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required).
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  5. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function
  6. Phase 2a cohorts only - Subjects with R/R MM who have been previously treated with prior BCMA-directed anti-myeloma therapy, achieved at least a partial response (PR) and progressed on the following treatment:
    1. Subjects who have received prior BCMA-directed CAR T-cell therapy. The last CAR T-cell therapy must have been received at least 6 months prior to JCARH125 screening.
    2. Subjects who have received prior BCMA-directed T-cell engager therapy.
    3. Subjects who have received prior BCMA-directed antibody-drug conjugate therapy.

Exclusion Criteria:

  1. Subjects with known active or history of CNS involvement by malignancy
  2. Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL); Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
  3. Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant
  4. History of another primary malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.
  5. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor [IL-6R])
  6. Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for subjects enrolled in Phase 2a cohorts)
  7. Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in Phase 2a cohorts)
  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. Untreated or active infection at time of initial screening, at the time of leukapheresis, within 72 hrs before lymphodepletion, or 5 days before JCARH125 infusion.
  10. History of any of the following cardiovascular conditions within 6 months of screening: Class III or IV heart failure as defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac disease
  11. Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to subjects in Phase 1 Anakinra Cohort)
  12. History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Verified Winship Cancer Institute of Emory University
Verified John Theurer Cancer Center Hackensack Meridian Health
Verified Memorial Sloan Kettering Cancer Center
Verified Medical College of Wisconsin Froedtert Hospital

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Mayo Clinic (Rochester)

Rochester, MN

Methodist Hospital

San Antonio, TX

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Alabama
California
Colorado
Georgia
Verified Winship Cancer Institute of Emory University

SparkCures Verified Accurate, up-to-date information. Learn more

Illinois
Kansas
Maryland
Massachusetts
Michigan
Minnesota
Mayo Clinic (Rochester)

Rochester, MN

New Jersey
Verified John Theurer Cancer Center Hackensack Meridian Health

SparkCures Verified Accurate, up-to-date information. Learn more

New York
Verified Memorial Sloan Kettering Cancer Center

SparkCures Verified Accurate, up-to-date information. Learn more


Oregon
Texas
Methodist Hospital

San Antonio, TX

Washington
Wisconsin
Verified Medical College of Wisconsin Froedtert Hospital

SparkCures Verified Accurate, up-to-date information. Learn more

Published Results

ASCO 2020 Interim Results (EVOLVE)

May 29, 2020

  • Orva-cel's phase I/II Evolve trial now has 62 evaluable subjects, 22 of whom are said to have had a complete remission, with a further 35 in partial remission.
  • Overall Response Rate (ORR) 92%.

Resources

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