2023-509848-10-00招募中3 期
A Phase 3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of bb2121 Versus Standard Regimens in Subjects with Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 14
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Compare the efficacy of bb2121 to standard regimens in subjects with RRMM as measured by progression-free survival (PFS)
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
- •Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.
- •Adequate vascular access for leukapheresis.
- •Adequate contraceptive measures as outlined in the protocol.
- •Only subjects that would be considered for any of the 5 proposed standard regimens (DPd, DVd, IRd, Kd or EPd), as judged by the Investigator, should be included in the study.
- •Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements within this protocol and for a subject randomized to Treatment Arm A, subject agrees to continued follow-up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials.
- •Subject has measurable disease, defined as: • M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or • Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Subject has received at least 2 but no greater than 4 prior MM regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered as one regimen.
- •Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.
- •Subject must be refractory to the last treatment regimen. Refractory is defined as documented progressive disease during or within 60 days (measured from the last dose of any drug within the regimen) of completing treatment with the last anti-myeloma regimen before study entry.
- •Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
- •Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. Note that forced expiratory testing (FEV1) is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is < 50% of predicted normal.
- •Subject has a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
- •Subject was treated with DARA in combination with POM with or without dexamethasone (DP±d) as part of their most recent antimyeloma treatment regimen, cannot receive DPd as bridging therapy but may receive DVd , IRd, Kd or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
- •Subject was treated with DP±d as part of their most recent antimyeloma treatment regimen, cannot receive DPd if randomized to Treatment Arm B but may receive DVd, IRd, Kd or EPd as per Investigator's discretion.
- •Subject was treated with DARA in combination with BTZ with or without dexamethasone (DV±d) as part of their most recent antimyeloma treatment regimen, cannot receive DVd as bridging therapy but may receive DPd, IRd, Kd or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
- •Subject was treated with DV±d as part of their most recent antimyeloma treatment regimen, cannot receive DVd if randomized to Treatment Arm B but may receive DPd, IRd, Kd or EPd as per Investigator's discretion.
- •Subject was treated with IXA in combination with LEN with or without dexamethasone (IR±d) as part of their most recent antimyeloma treatment regimen, cannot receive IRd as bridging therapy but may receive DPd, DVd, Kd or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A. Refer to protocol for additional exclusion criteria
- •Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- •Subject has any condition that confounds the ability to interpret data from the study.
- •Subject has nonsecretory MM.
- •Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) < 1,000/μL b. Platelet count: < 75,000/μL in subjects in whom < 50% of bone marrow nucleated cells are plasma cells and platelet count < 50,000/μL in subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells (it is not permissible to transfuse a subject to reach this level) c. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level) d. Serum creatinine clearance (CrCl) < 45 mL/min e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome h. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
- •Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.
- •Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies: • Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system) or prostate cancer that can be treated with curative intent
- •Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
- •Subject with known central nervous system (CNS) involvement with myeloma.
研究组 & 干预措施
idecabtagene vicleucel
Experimental
Participants receiving idecabtagene vicleucel
干预措施: idecabtagene vicleucel (Drug)
结局指标
主要结局
Progression-free survival (PFS)
Progression-free survival (PFS)
次要结局
- Overall Survival (OS)
- Overall Response Rate (ORR)
- Event-free Survival (EFS)
- Minimal Residual Disease (MRD)
- Complete Response (CR) Rate
- Duration of Response (DOR)
- Time to Response (TTR)
- Safety
- Pharmacokinetics (PK) – bb2121
- Primary Domains of Interest Health Related Quality of Life (HRQoL)
- Time to next anti-myeloma treatment
- Progression-free survival after next line therapy (PFS2)
研究者
GSM-CT
Scientific
Celgene Corp.
研究点 (14)
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