Study of bb2121 in Multiple Myeloma

NCT ID: NCT02658929

Last Updated: 2023-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-22
• Study Completion Date: 2022-09-22

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).

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: BIOLOGICAL

bb2121

Interventions

bb2121

bb2121

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genetix Biotherapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristen Hege, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Stanford Cancer Center

Stanford, California, United States

National Cancer Institute

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Mt. Sinai Medical Center Division of Hematology/Oncology

New York, New York, United States

Sarah Cannon Research Inst

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 31042825 (View on PubMed)

Lin Y, Raje NS, Berdeja JG, Siegel DS, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Massaro M, Petrocca F, Yeri A, Finney O, Caia A, Yang Z, Martin N, Campbell TB, Rytlewski J, Fuller J, Hege K, Munshi NC, Kochenderfer JN. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med. 2023 Sep;29(9):2286-2294. doi: 10.1038/s41591-023-02496-0. Epub 2023 Aug 17.

Reference Type: DERIVED

PMID: 37592106 (View on PubMed)

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

Other Identifiers

CRB-401

Identifier Type: -

Identifier Source: org_study_id