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Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
Bu açık etiketli, çok merkezli Faz 1/2 (Phase 1/2) çalışması, nükseden ve/veya tedaviye dirençli multipl miyelom (multiple myeloma) olan erişkinlerde B hücre olgunlaşma antijenini (B-cell maturation antigen, BCMA) hedefleyen CAR T hücre ürünü JCARH125'in güvenliğini ve etkililiğini değerlendirmektedir. Faz 1 (Phase 1) bölümünde önerilen doz belirlenmekte, Faz 2 (Phase 2) bölümünde bu dozda etkililik incelenmekte; ayrıca anakinra ile koruyucu tedavi alan katılımcılar ve daha önce BCMA'ya yönelik tedavi almış katılımcılar ayrı kohortlarda değerlendirilmektedir. Katılım için en az 3 önceki anti-miyelom tedavi rejimi almış olmak ve protokolde belirtilen tedavilere maruz kalmış, son tedaviye dirençli olmak gerekmektedir.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
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