Study of bb2121 in Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT02658929
• Recruitment Status: Completed
• First Posted: January 20, 2016
• Last Update Posted: January 23, 2023
• Sponsor: Celgene
• Collaborator: bluebird bio
• Information provided by (Responsible Party): Celgene

Study Description

Brief Summary:

Study CRB-401 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb2121 in adults with relapsed/refractory multiple myeloma (MM).

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: bb2121	Phase 1

Detailed Description:

This is a 2-part, non-randomized, open label, multi-site Phase 1 study. the study design consists of 2 parts: Part A (Dose Escalation), in which the RP2D is determined, and Part B (Expansion Cohorts), in which subjects are treated with the determined RP2D.

Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (bb2121). Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. All subjects who have received bb2121 infusion will be followed for up to 60 months on CRB-401.

All subjects who complete the study, as well as those who withdraw from the study after receiving bb2121 for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo long-term follow-up in a companion study for up to 15 years after their last bb2121 infusion, with a focus on long-term safety and efficacy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CRB-401 A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma
• Actual Study Start Date: December 22, 2015
• Actual Primary Completion Date: July 22, 2019
• Actual Study Completion Date: September 22, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Biological: bb2121; bb2121

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs) [ Time Frame: Day 1 through Month 60 ]

Secondary Outcome Measures :

1. Disease-specific response criteria including: overall response rate (ORR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM. [ Time Frame: Day 1 through Month 60 ]
   Percentage of subjects who achieved a CR, VGR, PR according to IMWG Uniform Response Criteria for Multiple Myeloma (MM).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18 years of age at the time of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Subjects must have measurable disease including at least one of the criteria below:

Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment and refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. All sexually active males subjects must refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion.

Part A:

Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents

- Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy

Exclusion Criteria:

• Subjects with known central nervous system disease
• Inadequate hepatic function
• Inadequate renal function
• Inadequate bone marrow function
• Presence of active infection within 72 hours
• Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
• Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission
• Subjects with a history of class III or IV congestive heart failure or non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 6 months
• Known human immunodeficiency virus (HIV) positivity
• Subjects who have plasma cell leukemia or clinically significant amyloidosis
• Pregnant or lactating women

Contacts and Locations

Locations

United States, California

Stanford Cancer Center

Stanford, California, United States, 94305

United States, Maryland

National Cancer Institute

Bethesda, Maryland, United States, 20892

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Mt. Sinai Medical Center Division of Hematology/Oncology

New York, New York, United States, 10029

United States, Tennessee

Sarah Cannon Research Inst

Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

Celgene

bluebird bio

Investigators

• Study Director: Kristen Hege, MD; Celgene Corporation

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

Publications:

Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, Petrocca F, Quigley MT, Munshi N, Kochenderfer JN. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737. doi: 10.1056/NEJMoa1817226.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT02658929
• Other Study ID Numbers: CRB-401
• First Posted: January 20, 2016
• Last Update Posted: January 23, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Celgene:

Multiple Myeloma; Efficacy and Safety; bb2121; CAR T Cell; BCMA

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Idecabtagene vicleucel; Antineoplastic Agents, Immunological; Antineoplastic Agents