Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

NCT03651128 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: BB2121-MM-003U1111-1217-99882018-001023-38
• Study Type: interventional
• Target: 381
• Locations: 13 countries
• Sites: 60

Brief Summary

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM). The study is anticipated to randomize approximately 381 subjects with RRMM. Approximately 254 subjects will be randomized to Treatment Arm A and approximately 127 subjects will be randomized to Treatment Arm B.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; bb2121; Relapsed and Refractory Multiple Myeloma; High Risk Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Time from randomization to the first documentation of progressive disease based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma assessed by an independent response committee (IRC) or death due to any cause, whichever occurs first.

  Minimum of 5 years from randomization

Secondary Outcomes (18)

• Overall Survival (OS)

  Minimum of 5 years from randomization

• Event-free Survival (EFS)

  Minimum of 5 years from randomization

• Overall Response Rate (ORR)

  Minimum of 5 years from randomization

• Minimal Residual Disease (MRD)

  Minimum of 5 years from randomization

• Complete Response (CR) Rate

  Minimum of 5 years from randomization

Study Arms (2)

Arm A - Administration of bb2121

EXPERIMENTAL

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

Arm B- standard regimens as per Investigator's discretion

EXPERIMENTAL

The participants will receive one of following regimens dependent on the subject's most recent anti-myeloma treatment regimen: * Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (dex) (DPd) OR * DARA in combination with bortezomib (BTZ) and low-dose dex (DVd) OR * Ixazomib (IXA) in combination with lenalidomide (LEN) and low-dose dex (IRd) OR * Carfilzomib (CFZ) in combination with low-dose dexamethasone (Kd) OR * Elotuzumab (ELO) in combination with POM and low-dose dexamethasone (EPd)

Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Bortezomib; Drug: Ixazomib; Drug: Lenalidomide; Drug: Carfilzomib; Drug: Elotuzumab

Interventions

bb2121 BIOLOGICAL

bb2121

Arm A - Administration of bb2121

Daratumumab DRUG

Daratumumab

Arm B- standard regimens as per Investigator's discretion

Pomalidomide DRUG

Pomalidomide

Arm B- standard regimens as per Investigator's discretion

Dexamethasone DRUG

Dexamethasone

Arm B- standard regimens as per Investigator's discretion

Bortezomib DRUG

Bortezomib

Arm B- standard regimens as per Investigator's discretion

Ixazomib DRUG

Ixazomib

Arm B- standard regimens as per Investigator's discretion

Lenalidomide DRUG

Lenalidomide

Arm B- standard regimens as per Investigator's discretion

Carfilzomib DRUG

Carfilzomib

Arm B- standard regimens as per Investigator's discretion

Elotuzumab DRUG

Elotuzumab

Arm B- standard regimens as per Investigator's discretion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements within this protocol and for a subject randomized to Treatment Arm A, subject agrees to continued follow-up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials.
• Subject has documented diagnosis of MM and measurable disease, defined as:
• M-protein (serum protein electrophoresis \[sPEP\] or urine protein electrophoresis \[uPEP\]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Subject has received at least 2 but no greater than 4 prior MM regimens.
• Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.
• Subject must be refractory to the last treatment regimen. Refractory is defined as documented progressive disease during or within 60 days (measured from the last dose of any drug within the regimen) of completing treatment with the last anti-myeloma regimen before study entry.
• Subject achieved a response (minimal response \[MR\] or better) to at least 1 prior treatment regimen.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.
• Adequate vascular access for leukapheresis
• Females of childbearing potential (FCBP) must:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has nonsecretory multiple myeloma (MM).
• Subject has any of the following laboratory abnormalities:
• a. Absolute neutrophil count (ANC) \< 1,000/μL b. Platelet count: \< 75,000/μL in subjects in whom \< 50% of bone marrow nucleated cells are plasma cells and platelet count \< 50,000/μL in subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells (it is not permissible to transfuse a subject to reach this level) c. Hemoglobin \< 8 g/dL (\< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level) d. Serum creatinine clearance (CrCl) \< 45 mL/min e. Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × upper limit of normal (ULN) g. Serum total bilirubin \> 1.5 × ULN or \> 3.0 mg/dL for subjects with documented Gilbert's syndrome h. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \> 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
• Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) \< 92% on room air.
• Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years • Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system) or prostate cancer that can be treated with curative intent
• Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis.
• Subject with known central nervous system (CNS) involvement with myeloma.

Sponsors & Collaborators

• Celgene: lead

Study Sites (60)

Local Institution - 109

Birmingham, Alabama, 10016, United States

Location

Local Institution - 141

Scottsdale, Arizona, 85259, United States

Location

Local Institution - 145

Los Angeles, California, 90048, United States

Location

Local Institution - 122

Los Angeles, California, 90095, United States

Location

Local Institution - 124

Palo Alto, California, 94304, United States

Location

Local Institution - 142

Aurora, Colorado, 80045, United States

Location

Local Institution - 108

Jacksonville, Florida, 32224, United States

Location

Local Institution - 102

Tampa, Florida, 33612, United States

Location

Local Institution - 131

Atlanta, Georgia, 30322, United States

Location

Local Institution - 140

Atlanta, Georgia, 30342, United States

Location

Local Institution - 139

Chicago, Illinois, 60611, United States

Location

Local Institution - 100

Indianapolis, Indiana, 46202-528, United States

Location

Local Institution - 112

Westwood, Kansas, 66205-2003, United States

Location

Local Institution - 104

Baltimore, Maryland, 21201-1595, United States

Location

Local Institution - 134

Boston, Massachusetts, 02114, United States

Location

Local Institution - 123

Boston, Massachusetts, 02215, United States

Location

University Of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-5936, United States

Location

Local Institution - 125

Rochester, Minnesota, 55905-0001, United States

Location

Local Institution - 114

St Louis, Missouri, 63110, United States

Location

Local Institution - 138

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 119

New York, New York, 10029, United States

Location

Local Institution - 115

New York, New York, 10065, United States

Location

Local Institution - 135

New York, New York, 10065, United States

Location

Local Institution - 113

Durham, North Carolina, 27705, United States

Location

Local Institution - 111

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 110

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center William M. Cooper Ambulatory Care Pavillion

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 106

Nashville, Tennessee, 37203, United States

Location

Local Institution - 118

Dallas, Texas, 75246, United States

Location

Local Institution - 103

Dallas, Texas, 75390, United States

Location

Local Institution - 132

Houston, Texas, 77030, United States

Location

Local Institution - 136

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 105

Seattle, Washington, 98104, United States

Location

Local Institution - 107

Madison, Wisconsin, 53792, United States

Location

Local Institution - 202

Leuven, 3000, Belgium

Location

Local Institution - 302

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 303

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 402

Lille, 59037, France

Location

Local Institution - 403

Nantes, 44093, France

Location

Local Institution - 400

Paris, 75010, France

Location

Local Institution - 401

Toulouse, 31059, France

Location

Local Institution - 515

Cologne, 50937, Germany

Location

Local Institution - 513

Düsseldorf, 40225, Germany

Location

Local Institution - 514

Hamburg, 20246, Germany

Location

Local Institution - 512

Heidelberg, 69120, Germany

Location

Local Institution - 511

Würzburg, 97080, Germany

Location

Local Institution - 611

Bologna, 40138, Italy

Location

Local Institution - 806

Bunkyō City, 113-8677, Japan

Location

Local Institution - 804

Isehara City, Kanagawa, 259-1193, Japan

Location

Local Institution - 807

Nagoya, 467-8602, Japan

Location

Local Institution - 805

Shibuya-ku, 150-8935, Japan

Location

Local Institution - 650

Amsterdam, 1081 HV, Netherlands

Location

Local Institution - 651

Rotterdam, 3015 CN, Netherlands

Location

Local Institution - 700

Oslo, N-0027, Norway

Location

Local Institution - 750

Pamplona, 31008, Spain

Location

Local Institution - 751

Salamanca, 37007, Spain

Location

Local Institution - 800

Stockholm, SE-141 86, Sweden

Location

Local Institution - 251

Bern, 3010, Switzerland

Location

Local Institution - 850

Leeds, LS9 7TF, United Kingdom

Location

Local Institution - 851

London, SE5 9RS, United Kingdom

Location

Related Publications (4)

• Lopez-Munoz N, Bar N, Diels J, van Sanden S, Mendes J, Lee S, Hernando T, Lendvai N, Patel N, Ishida T, Er J, Harrison SJ. Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2-4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison. Adv Ther. 2026 Feb 2. doi: 10.1007/s12325-025-03479-y. Online ahead of print.

  PMID: 41627370 DERIVED

• Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon S, Abrahamsen IW, Baz R, Broijl A, Chen C, Jagannath S, Raje N, Scheid C, Delforge M, Benjamin R, Pabst T, Iida S, Berdeja J, Giralt S, Truppel-Hartmann A, Chen Y, Zhong X, Wu F, Piasecki J, Eliason L, Dhanda D, Felten J, Caia A, Cook M, Popa McKiver M, Rodriguez-Otero P. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood. 2024 Dec 5;144(23):2389-2401. doi: 10.1182/blood.2024024582.

  PMID: 39197072 DERIVED

• Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon SR, Delforge M, Berdeja J, Truppel-Hartmann A, Yang Z, Favre-Kontula L, Wu F, Piasecki J, Cook M, Giralt S. Plain language summary of the KarMMa-3 study of ide-cel or standard of care regimens in people with relapsed or refractory multiple myeloma. Future Oncol. 2024;20(18):1221-1235. doi: 10.2217/fon-2023-0954. Epub 2024 Apr 23.

  PMID: 38651976 DERIVED

• Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon SR, Delforge M, Berdeja J, Truppel-Hartmann A, Yang Z, Favre-Kontula L, Wu F, Piasecki J, Cook M, Giralt S. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023 Mar 16;388(11):1002-1014. doi: 10.1056/NEJMoa2213614. Epub 2023 Feb 10.

  PMID: 36762851 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

idecabtagene vicleucel; daratumumab; pomalidomide; Dexamethasone; Bortezomib; ixazomib; Lenalidomide; carfilzomib; elotuzumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 29, 2018
• Study Start: April 16, 2019
• Primary Completion (Estimated): April 8, 2027
• Study Completion (Estimated): April 8, 2027
• Last Updated: December 15, 2022

Record last verified: 2022-12

Locations

DE (5); FR (4); NL (2); CH (1); IT (1); US (34); ES (2); BE (1); CA (2); SE (1); JP (4); NO (1); GB (2)