Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma

NCT04855136 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: BB2121-MM-0072020-003248-10
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 17

Brief Summary

This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in combination with other therapies in adult subjects with R/RMM. The following combinations will be

• Arm A will test bb2121 in combination with CC-220 (± low-dose dexamethasone)
• Arm B will test bb2121 in combination with BMS-986405 (JSMD194) Combination agents being tested may be administered before, concurrently with and/or following (ie, maintenance) bb2121 infusion. The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.

Conditions

Multiple Myeloma

Keywords

Relapsed/Refractory Multiple Myeloma; BB2121; ide-cel; CC-220; JSMD194; BMS-986405; DPd; PVd; CAR T; KarMMa-7; Phase I; Phase II; DARA; POM; BTZ

Outcome Measures

Primary Outcomes (2)

• Does Limiting Toxicity (DLT) rates _Phase 1

  Percentage of participants experiencing DLTs

  Up to 28 days from start of the combination therapy

• Complete Response Rate (CRR)_ Phase 2

  Proportion of participants who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by investigator's review

  Up to 24 months

Secondary Outcomes (14)

• Incidence of Adverse Event (AEs)

  Up to 24 months after the last participant received any study treatment

• Overall Response Rate (ORR)

  Up to 24 months after the last participant received any study treatment in the respective cohort

• Progression-free Survival (PFS)

  Up to 24 months after the last participant received any study treatment in the respective cohort

• Overall Survival (OS)

  Up to 24 months after the last participant received any study treatment in the respective cohort

• Time to response (TTR)

  Up to 24 months after the last participant received any study treatment in the respective cohort

Study Arms (2)

Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)

EXPERIMENTAL

bb2121 will be administered at a target dose of 450 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.

Biological: BB2121; Drug: CC-220

Arm B- bb2121 in combination with BMS-986405 (JSMD194)

EXPERIMENTAL

* bb2121 will be administered at a target dose of 450 x 10\^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion * Enrollment is closed for this Arm

Biological: BB2121; Drug: BMS-986405

Interventions

BB2121 BIOLOGICAL

CAR T Cell Therapy

Also known as: ide-cel

Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone); Arm B- bb2121 in combination with BMS-986405 (JSMD194)

CC-220 DRUG

Cereblon (CRBN) E3 ligase modulatory compound (CELMoD)

Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)

BMS-986405 DRUG

gamma secretase inhibitor (GSI)

Also known as: JSMD194

Arm B- bb2121 in combination with BMS-986405 (JSMD194)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• Participant has documented diagnosis of MM and measurable disease, defined as:
• M-protein (serum protein electrophoresis \[sPEP ≥ 0.5 g/dL\] or urine protein electrophoresis \[uPEP\]): 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
• Participant has received:
• at least 3 prior MM regimens for Arm A Cohort 1 and Arm B
• at least 1 but no greater than 3 prior MM regimens for Arm A Cohort 2
• Arm A Cohort 1 and Arm B: Participant has received prior treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody-containing regimen for at least 2 consecutive cycles.
• Arm A Cohort 2: Participant has received prior treatment with an immunomodulatory agent for at least 2 consecutive cycles.
• Evidence of PD during or within 6 months (measured from the last dose of any drug within the regimen) of completing treatment with the last antimyeloma regimen before study entry.
• Participant achieved a response (minimal response \[MR\] or better) to at least 1 prior treatment regimen.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• Participant has non-secretory MM or has history of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
• Participant has any of the following laboratory abnormalities:
• ANC and Platelets count as reported below
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L) (transfusion is not permitted within 21 days of screening)
• Creatinine clearance (CrCl) as reported below
• Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L)
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 ×upper limit of normal (ULN)
• Serum total bilirubin \> 1.5 × ULN or \> 3.0 mg/dL for participants with documented Gilbert's syndrome
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or participant requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
• Participant has inadequate pulmonary function defined as oxygen saturation (SaO2) \< 92% on room air.
• Participant has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
• Prior exposure to CC-220 (± low-dose dexamethasone) as part of their most recent antimyeloma treatment regimen (Arm A).
• Prior exposure to BMS-986405 (JSMD194) (Arm B).
• Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy.

Sponsors & Collaborators

• Celgene: lead

Study Sites (17)

Local Institution - 117

Birmingham, Alabama, 10016, United States

Location

Local Institution - 113

San Francisco, California, 94143, United States

Location

Local Institution - 101

Jacksonville, Florida, 32224-1865, United States

Location

Local Institution - 104

Atlanta, Georgia, 30322, United States

Location

Local Institution - 120

Atlanta, Georgia, 30342, United States

Location

Local Institution - 114

Chicago, Illinois, 60611, United States

Location

Local Institution - 108

Boston, Massachusetts, 02117, United States

Location

Local Institution - 124

Boston, Massachusetts, 02215, United States

Location

Local Institution - 109

Hackensack, New Jersey, 07601, United States

Location

New York University Langone

New York, New York, 10016, United States

Location

Local Institution - 110

New York, New York, 10032, United States

Location

Local Institution - 111

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 118

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 103

Nashville, Tennessee, 37203, United States

Location

Local Institution - 107

Houston, Texas, 77030, United States

Location

Local Institution - 201

Pamplona, 31008, Spain

Location

Local Institution - 202

Salamanca, 37007, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma

Interventions

idecabtagene vicleucel; iberdomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 22, 2021
• Study Start: June 1, 2021
• Primary Completion: April 25, 2025
• Study Completion: April 25, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (15); ES (2)