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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03361748
Recruitment Status : Completed
First Posted : December 5, 2017
Last Update Posted : February 1, 2024
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: bb2121 Phase 2

Detailed Description:
Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 149 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : December 18, 2017
Actual Primary Completion Date : December 20, 2023
Actual Study Completion Date : December 20, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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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).


Outcome Measures
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Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma.


Secondary Outcome Measures :
  1. Complete Response (CR) Rate [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma

  2. Time to Response [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of response

  3. Duration of Response [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time from first response to disease progression or death from any cause

  4. Progression-free Survival (PFS) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first

  5. Time to Progression (TTP) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of PD

  6. Overall Survival (OS) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time from first bb2121 infusion to time of death due to any cause

  7. Adverse Events (AEs) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Number of participants with adverse events (AEs), severity of adverse events, adverse events of special interest (AESI), and serious adverse events (SAEs)

  8. Pharmacokinetics - Cmax [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    The maximum transgene level at Tmax

  9. Pharmacokinetics - Tmax [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time to peak transgene level

  10. Pharmacokinetics - AUC [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Area under the curve of the transgene level

  11. Immunogenicity [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Development of an anti-CAR antibody response

  12. Minimal Residual Disease (MRD) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Proportion of MRD evaluable subjects that are MRD negative

  13. Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Questionnaire will be used as a measure of health-related quality of life

  14. Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire [ Time Frame: : Minimum of 24 months post-bb2121 infusion ]
    Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal

  15. Subject-reported outcomes as measured by EORTC-QLQ-MY20 [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03361748


Locations
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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03361748    
Other Study ID Numbers: BB2121-MM-001
U1111-1202-5554 ( Other Identifier: WHO )
2017-002245-29 ( EudraCT Number )
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: February 1, 2024
Last Verified: January 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
Multiple Myeloma
Efficacy and Safety
BB2121
 CAR T Cell
BCMA
Relapsed and Refractory
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
 Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Idecabtagene vicleucel
Antineoplastic Agents, Immunological
Antineoplastic Agents