Study of bb2121 in Multiple Myeloma identifier recruitment status First Posted Last update posted
NCT02658929 Active, not recruiting January 20, 2016 August 21, 2019

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: Multiple Myeloma
Intervention/treatment: Biological: bb2121
Phase: 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
Estimated Enrollment : 67 participants
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 2015
Estimated Primary Completion Date: November 2023
Estimated Study Completion Date: November 2023

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
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

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
United States, California Stanford Cancer Center Stanford
United States, Maryland National Cancer Institute Bethesda
United States, Massachusetts Massachusetts General Hospital Boston
United States, Massachusetts Beth Israel Deaconess Medical Center Boston
United States, Massachusetts Dana Farber Cancer Institute Boston
United States, Minnesota Mayo Clinic Rochester
United States, New Jersey Hackensack University Medical Center Hackensack
United States, New York Mt. Sinai Medical Center Division of Hematology/Oncology New York
United States, Tennessee Sarah Cannon Research Inst Nashville
Sponsors and Collaborators
bluebird bio
Study Director : Kristen Hege, MD Celgene Corporation
More Information
Other 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 Identifier : NCT02658929     
Other Study ID Numbers : CRB-401
First Posted : January 20, 2016
Last Update Posted : August 21, 2019
Last Verified : August 2019
Individual Participant
Data (IPD) Sharing
Plan to Share IPD: Undecided
Keywords provided by Celgene: bb2121
CAR T Cell
Multiple Myeloma
Efficacy and Safety
Additional relevant MeSH terms :
Multiple Myeloma
Neoplasms, Plasma Cell