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

A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

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.

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • Local Institution - 201
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven
• Canada
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 301
• France
  • Lille, France, 59037
    • Local Institution - 402
  • Nantes, France, 44093
    • Local Institution - 401
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59037
      • Centre Hospitalier Regional Universitaire de Lille-Hopital Calude Huriez Service des Maladies du Sang
  • Pays De La Loire
    • Nantes, Pays De La Loire, France, 44093
      • Centre Hospitalier Universitaire de Nantes - Hotel Dieu
• Germany
  • Heidelberg, Germany, 69120
    • Local Institution - 502
  • Tübingen, Germany, 72076
    • Local Institution - 503
  • Würzburg, Germany, 97080
    • Local Institution - 501
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitatsklinikum Heidelberg Medizinische Klinik Krehl-Klinik Haematologie, Onkologie, Rheumato
    • Tübingen, Baden-Württemberg, Germany, 72076
      • University of Tübingen
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Universitätsklinikum Würzburg
• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti di Bergamo
  • Bergamo, Italy, 24128
    • Local Institution - 602
  • Bologna, Italy, 40138
    • Local Institution - 601
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero Universitaria Di Bologna Policlinico
• Japan
  • Isehara City, Kanagawa, Japan, 259-1193
    • Local Institution - 803
  • Shibuya-ku, Japan, 150-8935
    • Local Institution - 801
  • Shimotsuke, Japan, 329-0498
    • Local Institution - 802
  • Shinjuku City, Japan, 162-8666
    • Local Institution - 804
  • Shinjuku City, Japan, 162-8666
    • Tokyo Women's Medical University Hospital
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 3290498
      • Jichi Medical University Hospital
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Japan Red Cross Medical Center
• Spain
  • Badalona (Barcelona), Spain, 08916
    • Local Institution - 702
  • Pamplona, Spain, 31008
    • Local Institution - 701
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol Can Ruti
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California - San Francisco
    • San Francisco, California, United States, 94143
      • Local Institution - 108
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 103
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 107
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 106
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 105
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 102
  • New York
    • New York, New York, United States, 10029
      • Local Institution - 109
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 101
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75390
      • Local Institution - 104

Participation Criteria

Eligibility Criteria

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

Description

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.

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: 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.	Biological: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Number of participants who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an independent response committee (IRC).	From first dose to 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	Percentage of participants who achieved CR or sCR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC.	From first dose to 24 Months
Time to Response	Time from first bb2121 infusion to first documentation of response of PR or better.	From first dose to initial response (approximately on average 1.2 months, max of 8.8 months)
Duration of Response	Time from first documentation of response or PR or better to first documentation of disease progression or death from any cause, whichever occurs first.	From first dose to 24 months after first dose
Progression Free Survival (PFS)	Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.	From first dose to 24 months after first dose
Time to Progression (TTP)	Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.	From first dose to 24 months after first dose
Overall Survival	Time from first bb2121 infusion to time of death due to any cause.	From screening to the end of follow up (approximately 5 years and 2 months)
Number of Participants With Safety Related Events	Number of participants with adverse events (AEs), adverse events of special interest (AESI), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, infection and clinically signifcant laboratory abnormalities.	From screening to the end of follow up (approximately 5 years and 2 months)
Cmax	Cmax is defined as the maximum transgene level at Tmax Tmax: The time of maximum observed transgene level, obtained directly from the observed transgene level - time.	From first dose to the end of follow up (Approximately 5 years)
AUC 0-9M	The AUC of the transgene level from the time of dosing to 9 months	at 9 months post first dose (Approximtately 9 Months)
Tmax	Tmax: The time of maximum observed transgene level, obtained directly from the observed transgene level - time.	From first dose to the end of follow up (Approximately 5 years)
Number of Participants With Anti-CAR-Antibodies	Number of Participants with Anti-CAR-Antibodies. Pre-postive is defined by last value before or on bb2121 infusion date is positive Post-positve is defined by at least one positive value post bb2121 infusion.	From first dose to the end of follow up (Approximately 5 years)
Percentage of Participants Who Achieved >= VGPR and MRD Negative Status	Percentage of participants who achieved ≥ VGPR and MRD negative status at a sensitivity of 10-⁵ at any time point within 3 months prior to achieving at least VGPR until the time of PD/death. MRD in the bone marrow will be measured using both next generation sequencing (NGS) techniques measuring immunoglobulin gene rearrangements of the malignant clone. MRD will be reported with a sensitivity of 10-⁴, 10-⁵, and 10-⁶ nucleated cells. The primary analysis for MRD negative response will use the sensitivity of 10-⁵. MRD = Minimal Residual Disease PD = Progressive Disease VGPR = Very good partial response.	From screening to the end of follow up (Approximately 5 years and 2 months)
Mean Change From Baseline on the EORTC QLQ-C30 - Fatigue.	Mean change from baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) The QLQ-C30 employs a week recall period for all items. All items will be scored from 0 to 100. The average of the scores will represent the symptoms score. A high score for a symptom scale/item represents a high level of symptomatic problem.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-C30 - Pain	Mean change from baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) The QLQ-C30 employs a week recall period for all items. All items will be scored from 0 to 100. The average of the scores will represent the symptoms score. A high score for a symptom scale/item represents a high level of symptomatic problem.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-C30 - Physical Functioning	The QLQ-C30 employs a week recall period for all items. All items will be scored from 0 to 100 and an average will be taken. This average is the overall score. A higher scale score represents a higher level of well-being and better ability of daily functioning. Thus, a high score for a functional scale represents a high/healthy level of functioning.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-C30 - Cognitive Functioning	The QLQ-C30 employs a week recall period for all items. All items will be scored from 0 to 100 and an average will be taken. This average is the overall score. A higher scale score represents a higher level of well-being and better ability of daily functioning. Thus, a high score for a functional scale represents a high/healthy level of functioning.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-C30 - Global Heath/QoL	Mean change from baseline on the EORTC QLQ-C30 The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A higher scale score represents a higher level of well-being and better ability of daily functioning. Thus, a high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/HRQoL represents a high HRQoL.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-MY20 - Disease Symptoms	Mean change from baseline on the EORTC QLQ-MY20 The EORTC has developed a myeloma module referred to as QLQ- MY20, to be administered alongside the core QLQ-C30. The QLQ-MY20 is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality. All items will be scored from 0 to 100. The average of the scores will represent the symptoms score. A high score for a symptom scale/item represents a high level of symptomatic problem.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EORTC QLQ-MY20 - Side Effects	Mean change from baseline on the EORTC QLQ-MY20 The EORTC has developed a myeloma module referred to as QLQ- MY20, to be administered alongside the core QLQ-C30. The QLQ-MY20 is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality. All items will be scored from 0 to 100. The average of the scores will represent the symptoms score. A high score for a symptom scale/item represents a high level of symptomatic problem.	At Day 1 and at specific time points up to month 24
Mean Change From Baseline on the EQ-5D-5L Index	The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.530 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points.	At Day 1 and at specific time points up to month 24

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb; Study Director: Kristen Hege, Celgene

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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Efficacy and Safety; CAR T Cell; BCMA; Relapsed and Refractory; BB2121
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Idecabtagene vicleucel
• Other Study ID Numbers: BB2121-MM-001; U1111-1202-5554 (Other Identifier: WHO); 2017-002245-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No