Multiple Myeloma Clinical Trial
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
Summary
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.
Eligibility Criteria
Key Inclusion Criteria:
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):
Autologous stem cell transplant
A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination
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.
Subjects must have measurable disease.
Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required).
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function
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:
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.
Subjects who have received prior BCMA-directed T-cell engager therapy.
Subjects who have received prior BCMA-directed antibody-drug conjugate therapy.
Exclusion Criteria:
Subjects with known active or history of CNS involvement by malignancy
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
Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant
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.
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])
Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for subjects enrolled in Phase 2a cohorts)
Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in Phase 2a cohorts)
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
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.
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
Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to subjects in Phase 1 Anakinra Cohort)
History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study
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There are 20 Locations for this study
Birmingham Alabama, 10016, United States
Duarte California, 91010, United States
Los Angeles California, 90095, United States
San Francisco California, 94158, United States
Denver Colorado, 80218, United States
Atlanta Georgia, 30322, United States
New Lenox Illinois, 60451, United States
Indianapolis Indiana, 46202, United States
Westwood Kansas, 66205, United States
Baltimore Maryland, 21231, United States
Boston Massachusetts, 02114, United States
Detroit Michigan, 48201, United States
Rochester Minnesota, 55905, United States
Hackensack New Jersey, 07601, United States
Buffalo New York, 14263, United States
New York New York, 10065, United States
Portland Oregon, 97201, United States
Seattle Washington, 98104, United States
Seattle Washington, 98109, United States
Milwaukee Wisconsin, 53226, United States
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