Clinical Trials/NCT03651128

NCT03651128

Active, not recruiting

Phase 3

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)

Celgene60 sites in 7 countries381 target enrollmentApril 16, 2019

ConditionsMultiple Myeloma

Interventionsbb2121 Daratumumab Pomalidomide Dexamethasone Bortezomib Ixazomib Lenalidomide Carfilzomib Elotuzumab

DrugsDaratumumab Pomalidomide Dexamethasone Bortezomib Ixazomib Lenalidomide Carfilzomib Elotuzumab

Overview

Phase: Phase 3
Intervention: bb2121
Conditions: Multiple Myeloma
Sponsor: Celgene
Enrollment: 381
Locations: 60
Primary Endpoint: Progression-free Survival (PFS)
Status: Active, not recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM).

The study is anticipated to randomize approximately 381 subjects with RRMM. Approximately 254 subjects will be randomized to Treatment Arm A and approximately 127 subjects will be randomized to Treatment Arm B.

Registry

clinicaltrials.gov

Start Date

April 16, 2019

End Date

April 8, 2027

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Celgene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must satisfy the following criteria to be enrolled in the study:
•Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
•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 documented diagnosis of MM and 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 (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
•Subject has received at least 2 but no greater than 4 prior MM regimens.
•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.

Exclusion Criteria

•The presence of any of the following will exclude a subject from enrollment:
•Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
•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 multiple myeloma (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 • Basal cell carcinoma of the skin
•Squamous cell carcinoma of the skin

Arms & Interventions

Arm A - Administration of bb2121

bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy

Intervention: bb2121

Arm B- standard regimens as per Investigator's discretion

The participants will receive one of following regimens dependent on the subject's most recent anti-myeloma treatment regimen: * Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (dex) (DPd) OR * DARA in combination with bortezomib (BTZ) and low-dose dex (DVd) OR * Ixazomib (IXA) in combination with lenalidomide (LEN) and low-dose dex (IRd) OR * Carfilzomib (CFZ) in combination with low-dose dexamethasone (Kd) OR * Elotuzumab (ELO) in combination with POM and low-dose dexamethasone (EPd)

Intervention: Daratumumab

Arm B- standard regimens as per Investigator's discretion

Intervention: Pomalidomide

Arm B- standard regimens as per Investigator's discretion

Intervention: Dexamethasone

Arm B- standard regimens as per Investigator's discretion

Intervention: Bortezomib

Arm B- standard regimens as per Investigator's discretion

Intervention: Ixazomib

Arm B- standard regimens as per Investigator's discretion

Intervention: Lenalidomide

Arm B- standard regimens as per Investigator's discretion

Intervention: Carfilzomib

Arm B- standard regimens as per Investigator's discretion

Intervention: Elotuzumab

Outcomes

Primary Outcomes

Progression-free Survival (PFS)

Time Frame: Minimum of 5 years from randomization

Time from randomization to the first documentation of progressive disease based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma assessed by an independent response committee (IRC) or death due to any cause, whichever occurs first.

Secondary Outcomes

Pharmacokinetics- tmax(Minimum 5 years after bb2121 infusion)
Pharmacokinetics- AUC(Minimum 5 years after bb2121 infusion)
Pharmacokinetics- Cmax(Minimum 5 years after bb2121 infusion)
Overall Survival (OS)(Minimum of 5 years from randomization)
Event-free Survival (EFS)(Minimum of 5 years from randomization)
Overall Response Rate (ORR)(Minimum of 5 years from randomization)
Minimal Residual Disease (MRD)(Minimum of 5 years from randomization)
Complete Response (CR) Rate(Minimum of 5 years from randomization)
Duration of Response (DOR)(Minimum of 5 years from randomization)
Adverse Events (AEs)(Minimum of 5 years from randomization)
Time to Response (TTR)(Minimum of 5 years from randomization)
Pharmacokinetics- t-last(Minimum 5 years after bb2121 infusion)
Pharmacokinetics- AUC0-28days(Minimum 5 years after bb2121 infusion)
Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30)(Minimum of 5 years from randomization)
Subject-reported outcomes as measured by EuroQoL Group European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) Health Questionnaire(Minimum of 5 years from randomization)
Subject-reported outcomes as measured by European Quality of Life Multiple Myeloma Module (EORTC-QLQ-MY20)(Minimum of 5 years from randomization)
Time to next antimyeloma treatment(Minimum of 5 years from randomization)
Progression-free survival after next line therapy (PFS2)(Minimum of 5 years from randomization)