Study of bb2121 in Multiple Myeloma

CRB-401 A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma

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).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: bb2121

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 Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center Division of Hematology/Oncology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Inst

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Percentage of subjects who achieved a CR, VGR, PR according to IMWG Uniform Response Criteria for Multiple Myeloma (MM).	Day 1 through Month 60

Collaborators and Investigators

• Sponsor: Celgene
• Collaborators: bluebird bio

Publications and helpful links

General 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): July 22, 2019
• Study Completion (Actual): September 22, 2022

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: January 15, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Efficacy and Safety; CAR T Cell; BCMA; bb2121
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CRB-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided