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

Phase 1TerminatedNCT04855136

Celgene21 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Participants must satisfy the following criteria to be enrolled in the study: * Participant has documented diagnosis of MM and measurable disease, defined as: 1. M-protein (serum protein electrophoresis \[sPEP ≥ 0.5 g/dL\] or urine protein electrophoresis \[uPEP\]): uPEP ≥ 200 mg/24 hours and/or 2. 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: 1. at least 3 prior MM regimens for Arm A Cohort 1 and Arm B 2. 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. Exclusion Criteria: 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: 1. ANC and Platelets count as reported below 2. Hemoglobin \< 8 g/dL (\< 4.9 mmol/L) (transfusion is not permitted within 21 days of screening) 3. Creatinine clearance (CrCl) as reported below 4. Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L) 5. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 ×upper limit of normal (ULN) 6. Serum total bilirubin \> 1.5 × ULN or \> 3.0 mg/dL for participants with documented Gilbert's syndrome 7. 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. * Treatment Arm A Cohort 1 and Arm B: participant has received autologous stem cell transplantation (ASCT) within 12 weeks prior to leukapheresis. * Treatment Arm A Cohort 2: participant has received autologous stem cell transplantation (ASCT) within 12 months prior to leukapheresis.

Locations (17)

Local Institution - 117

Birmingham, Alabama, United States

Local Institution - 113

San Francisco, California, United States

Local Institution - 101

Jacksonville, Florida, United States

Local Institution - 104

Atlanta, Georgia, United States

Local Institution - 120

Atlanta, Georgia, United States

Local Institution - 114

Chicago, Illinois, United States

Local Institution - 108

Boston, Massachusetts, United States

Local Institution - 124

Boston, Massachusetts, United States

Local Institution - 109

Hackensack, New Jersey, United States

New York University Langone

New York, New York, United States

...and 7 more locations

Outcomes

Primary Outcomes

Does Limiting Toxicity (DLT) rates _Phase 1

Percentage of participants experiencing DLTs

Time frame: 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

Time frame: Up to 24 months

Secondary Outcomes

Incidence of Adverse Event (AEs)

An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

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

Overall Response Rate (ORR)

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