Protocol H125001: An Open-Label Phase 1/2 Study of JCARH125, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma
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.
18 Years and up
Accepting Healthy Volunteers?
1. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory disease. Participants must have received at least 3 prior lines of therapy. 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:
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 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 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
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 protein, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
3. Subjects who are considered eligible to receive an autologous stem cell transplant
4. History of another primary malignancy that has not been in remission for at least 2 years. The following are exempt from the 2-year limit: non-melanoma skin cancer, completely resected Stage 1 solid tumor with low risk for recurrence, 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
7. Prior treatment with a BCMA-targeted agent
8. Prior allogeneic stem cell transplant
9. 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