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)
- Conditions
- Multiple myeloma (MM) with at least 2 prior therapies including an immunomodulatory (IMiD) compound and a proteasome inhibitor (PI) and demonstrated disease progression on or within 60 days of completion of the last therapy.MedDRA version: 16.1Level: HLTClassification code: 10028229Term: Multiple myelomas Class: 10029104MedDRA version: 21.1Level: LLTClassification code: 10067095Term: Multiple myeloma progression Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509848-10-00
- Lead Sponsor
- Celgene Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 386
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.
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 o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Compare the efficacy of bb2121 to standard regimens in subjects with RRMM as measured by progression-free survival (PFS);Secondary Objective: Evaluate the safety of bb2121 compared to standard regimens in subjects with RRMM, Evaluate additional efficacy parameters of bb2121 compared to standard regimens in subjects with RRMM, Characterize the expansion and persistence of chimeric antigen receptor (CAR) + T cells, in the peripheral blood (cellular kineticspharmacokinetics [PK]), Evaluate the percentage of subjects who attain minimal residual disease (MRD) negative status by next generation sequencing (NGS), Evaluate the impact of bb2121 compared to standard regimens on the changes in health-related quality of life (HRQoL), Evaluate the impact of bb2121 on health utility values compared with standard regimens;Primary end point(s): Progression-free survival (PFS)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Overall Response Rate (ORR);Secondary end point(s):Overall Survival (OS);Secondary end point(s):Event-free Survival (EFS);Secondary end point(s):Minimal Residual Disease (MRD);Secondary end point(s):Complete Response (CR) Rate;Secondary end point(s):Duration of Response (DOR);Secondary end point(s):Time to Response (TTR);Secondary end point(s):Safety;Secondary end point(s):Pharmacokinetics (PK) – bb2121;Secondary end point(s):Primary Domains of Interest Health Related Quality of Life (HRQoL);Secondary end point(s):Time to next anti-myeloma treatment;Secondary end point(s):Progression-free survival after next line therapy (PFS2)