Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

NCT ID: NCT03361748

Last Updated: 2025-05-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-13

Study Completion Date

2023-12-20

Brief Summary

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This is an open label, single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory multiple myeloma. A leukapheresis procedure will be performed to manufacture bb2121 chimeric antigen receptor (CAR) modified T cells. Prior to bb2121 infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide.

Detailed Description

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Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Administration of bb2121

bb2121 autologous CAR T cells will be infused at a dose ranging from 15 - 450 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy.

Group Type EXPERIMENTAL

bb2121

Intervention Type BIOLOGICAL

: bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA02 CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Interventions

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bb2121

: bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA02 CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

Eligibility is determined prior to leukapheresis. Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Documented diagnosis of multiple myeloma

* Must have received at least 3 prior MM treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.
* Must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen.
* Must have received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
* Must be refractory to the last treatment regimen.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. Subjects must have measurable disease, including at least one of the criteria below:

* Serum M-protein greater or equal to 1.0 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
5. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

1. Subjects with known central nervous system involvement with myeloma.
2. History or presence of clinically relevant central nervous system (CNS) pathology.
3. Subjects with active or history of plasma cell leukemia.
4. Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease
5. Inadequate organ function
6. Ongoing treatment with chronic immunosuppressants
7. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
8. Evidence of human immunodeficiency virus (HIV) infection.
9. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
10. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV)
11. Subjects with a history of class III or IV congestive heart failure (CHF) or severe non-ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months.
12. 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
13. Pregnant or lactating women.
14. Subject with known hypersensitivity to any component of bb2121 productThe presence of any of the following will exclude a subject from enrollment:

1\. Subjects with known central nervous system involvement with myeloma. 2. History or presence of clinically relevant central nervous system (CNS) pathology.

3\. Subjects with active or history of plasma cell leukemia. 4. Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease 5. Inadequate organ function 6. Ongoing treatment with chronic immunosuppressants 7. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy 8. Evidence of human immunodeficiency virus (HIV) infection. 9. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV) 10. Subjects with a history of class III or IV congestive heart failure (CHF) or severe non-ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months. 11. 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 12. Pregnant or lactating women. 13 Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, or tocilizumab.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Kristen Hege

Role: STUDY_DIRECTOR

Celgene

Locations

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Local Institution - 108

San Francisco, California, United States

Site Status

University of California - San Francisco

San Francisco, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Local Institution - 103

Atlanta, Georgia, United States

Site Status

Local Institution - 107

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Local Institution - 106

Boston, Massachusetts, United States

Site Status

Local Institution - 105

Rochester, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Local Institution - 102

Hackensack, New Jersey, United States

Site Status

Local Institution - 109

New York, New York, United States

Site Status

Mt. Sinai Medical Center

New York, New York, United States

Site Status

Local Institution - 101

Nashville, Tennessee, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Local Institution - 104

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Universitaire Ziekenhuizen Leuven

Leuven, Flemish Brabant, Belgium

Site Status

Local Institution - 201

Leuven, , Belgium

Site Status

Local Institution - 301

Toronto, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Centre Hospitalier Regional Universitaire de Lille-Hopital Calude Huriez Service des Maladies du Sang

Lille, Hauts-de-France, France

Site Status

Centre Hospitalier Universitaire de Nantes - Hotel Dieu

Nantes, Pays de la Loire Region, France

Site Status

Local Institution - 402

Lille, , France

Site Status

Local Institution - 401

Nantes, , France

Site Status

Universitatsklinikum Heidelberg Medizinische Klinik Krehl-Klinik Haematologie, Onkologie, Rheumato

Heidelberg, Baden-Wurttemberg, Germany

Site Status

University of Tübingen

Tübingen, Baden-Wurttemberg, Germany

Site Status

Universitatsklinikum Würzburg

Würzburg, Bavaria, Germany

Site Status

Local Institution - 502

Heidelberg, , Germany

Site Status

Local Institution - 503

Tübingen, , Germany

Site Status

Local Institution - 501

Würzburg, , Germany

Site Status

Azienda Ospedaliero Universitaria Di Bologna Policlinico

Bologna, Emilia-Romagna, Italy

Site Status

Local Institution - 602

Bergamo, , Italy

Site Status

Ospedali Riuniti di Bergamo

Bergamo, , Italy

Site Status

Local Institution - 601

Bologna, , Italy

Site Status

Tokai University Hospital

Isehara, Kanagawa, Japan

Site Status

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Site Status

Japan Red Cross Medical Center

Shibuya-ku, Tokyo, Japan

Site Status

Local Institution - 803

Isehara City, Kanagawa, , Japan

Site Status

Local Institution - 801

Shibuya-ku, , Japan

Site Status

Local Institution - 802

Shimotsuke, , Japan

Site Status

Local Institution - 804

Shinjuku, , Japan

Site Status

Tokyo Women's Medical University Hospital

Shinjuku, , Japan

Site Status

Hospital Universitari Germans Trias i Pujol Can Ruti

Badalona, Barcelona, Spain

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Local Institution - 702

Badalona (Barcelona), , Spain

Site Status

Local Institution - 701

Pamplona, , Spain

Site Status

Countries

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United States Belgium Canada France Germany Italy Japan Spain

References

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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)

Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Feb 25;384(8):705-716. doi: 10.1056/NEJMoa2024850.

Reference Type BACKGROUND
PMID: 33626253 (View on PubMed)

Sidana S, Ahmed N, Akhtar OS, Brazauskas R, Oloyede T, Bye M, Hansen D, Ferreri C, Freeman CL, Afrough A, Anderson LD Jr, Dhakal B, Dhanda D, Gowda L, Hashmi H, Harrison MJ, Kitali A, Landau H, Mirza AS, Patwardhan P, Qazilbash M, Usmani S, Patel K, Nishihori T, Ganguly S, Pasquini MC. Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood. 2025 Jul 10;146(2):167-177. doi: 10.1182/blood.2024026216.

Reference Type DERIVED
PMID: 40198886 (View on PubMed)

Delforge M, Otero PR, Shah N, Moshkovich O, Braverman J, Dhanda DS, Lanar S, Devlen J, Miera M, Gerould H, Campbell TB, Munshi NC. Analysis of patient-reported experiences up to 2 years after receiving idecabtagene vicleucel (ide-cel, bb2121) for relapsed or refractory multiple myeloma: Longitudinal findings from the phase 2 KarMMa trial. Leuk Res. 2023 Jun;129:107074. doi: 10.1016/j.leukres.2023.107074. Epub 2023 Apr 3.

Reference Type DERIVED
PMID: 37087950 (View on PubMed)

Connarn JN, Witjes H, van Zutphen-van Geffen M, de Greef R, Campbell TB, Hege K, Zhou S, Lamba M. Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1687-1697. doi: 10.1002/psp4.12922. Epub 2023 Feb 15.

Reference Type DERIVED
PMID: 36794354 (View on PubMed)

Karampampa K, Zhang W, Venkatachalam M, Cotte FE, Dhanda D. Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France. J Med Econ. 2023 Jan-Dec;26(1):243-253. doi: 10.1080/13696998.2023.2173466.

Reference Type DERIVED
PMID: 36705644 (View on PubMed)

Shah N, Mojebi A, Ayers D, Cope S, Dhanasiri S, Davies FE, Hari P, Patel P, Hege K, Dhanda D. Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. J Comp Eff Res. 2022 Jul;11(10):737-749. doi: 10.2217/cer-2022-0045. Epub 2022 Apr 29.

Reference Type DERIVED
PMID: 35485211 (View on PubMed)

Sharma P, Kanapuru B, George B, Lin X, Xu Z, Bryan WW, Pazdur R, Theoret MR. FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2022 May 2;28(9):1759-1764. doi: 10.1158/1078-0432.CCR-21-3803.

Reference Type DERIVED
PMID: 35046063 (View on PubMed)

Delforge M, Shah N, Miguel JSF, Braverman J, Dhanda DS, Shi L, Guo S, Yu P, Liao W, Campbell TB, Munshi NC. Health-related quality of life with idecabtagene vicleucel in relapsed and refractory multiple myeloma. Blood Adv. 2022 Feb 22;6(4):1309-1318. doi: 10.1182/bloodadvances.2021005913.

Reference Type DERIVED
PMID: 34933328 (View on PubMed)

Da Via MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterjee M, Meggendorfer M, Twardziok S, Goebeler ME, Topp MS, Hudecek M, Prommersberger S, Hege K, Kaiser S, Fuhr V, Weinhold N, Rosenwald A, Erhard F, Haferlach C, Einsele H, Kortum KM, Saliba AE, Rasche L. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med. 2021 Apr;27(4):616-619. doi: 10.1038/s41591-021-01245-5. Epub 2021 Feb 22.

Reference Type DERIVED
PMID: 33619368 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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U1111-1202-5554

Identifier Type: OTHER

Identifier Source: secondary_id

2017-002245-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BB2121-MM-001

Identifier Type: -

Identifier Source: org_study_id

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