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

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ClinicalTrials.gov Identifier: NCT03361748
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
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 13, 2017
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Administration of bb2121
bb2121 autologous CAR T cells will be infused at a dose ranging from 15 - 30 x 107 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).



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 ]
    Maximum peak in bb2121 CAR T CD3+ cells

  9. Pharmacokinetics - Tmax [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Time to peak of bb2121 CAR T CD3+ cells

  10. Pharmacokinetics - AUC [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Area under the curve of CAR T CD3+ cells

  11. Biomarker - Cytokines [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Cytokine induction in the blood of subjects after infusion of bb2121

  12. Biomarker - BCMA [ Time Frame: Minimum of 24 months post-bb2121 infusion ]
    Percentage and level of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood

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

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

  15. 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

  16. 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

  17. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

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 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 product

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


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
University of California - San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Mt. Sinai Medical Center Recruiting
New York, New York, United States, 10029
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Spain
Hospital Universitari Germans Trias i Pujol Can Ruti Recruiting
Badalona, Barcelona, Spain, 08916
Clinica Universidad de Navarra Recruiting
Pamplona, Navarre, Spain, 31008
Sponsors and Collaborators
Celgene
Investigators
Study Director: Kristen Hege Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03361748     History of Changes
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: March 27, 2018
Last Verified: March 2018

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:
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