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An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma Having Progressed Within One Year of Initial Treatment (KarMMa-2)

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ClinicalTrials.gov Identifier: NCT03601078
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

This study is a multi-cohort, open-label, multicenter Phase 2 study to determine the efficacy and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1) and in subjects with HR MM having progressed within one year of initial treatment (Cohort 2).

Approximately 122 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2 will enroll approximately 49 MM subjects with 1 prior anti-myeloma treatment regimen and HR disease defined as Stage III by the Revised International Staging System (R-ISS) and early relapse. The cohorts will start in parallel and independently.


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 : 122 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicohort, Open-label, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma Having Progressed Within One Year of Initial Treatment (KarMMa-2)
Estimated Study Start Date : November 13, 2018
Estimated Primary Completion Date : March 12, 2025
Estimated Study Completion Date : March 12, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: bb2121 in relapsed and refractory multiple myeloma patients
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
bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA 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)- Cohort 1 [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an independent response committee (IRC)

  2. Complete response (CR) rate - Cohort 2 [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC


Secondary Outcome Measures :
  1. Complete response (CR) rate - Cohort 1 [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC

  2. Overall response rate (ORR) - Cohort 2 [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC

  3. Time to response (TTR) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of response (PR or greater)

  4. Duration of response (DoR) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first

  5. Progression-free survival (PFS) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of PD, or death due to any cause, whichever occurs first

  6. Time to progression (TTP) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Time from first bb2121 infusion to first documentation of PD

  7. Overall survival (OS) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Time from first bb2121 infusion to time of death due to any cause

  8. Adverse Events (AEs) [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Type, frequency, seriousness and severity of adverse events (AEs), adverse events of special interest (AESIs) (including cytokine release syndrome, neurotoxicity and infection), and relationship of AE to study drug.

  9. Pharmacokinetics - Cmax [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells

  10. Pharmacokinetics - tmax [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Time to peak of bb2121 CAR T cells

  11. Pharmacokinetics - AUC [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Area under the curve of CAR T cells

  12. Pharmacokinetics - tlast [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Time to last measurable CAR T cells

  13. Pharmacokinetics - AUC0-28days [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Area under the curve of CAR T cells from time zero to Day 28

  14. Immunogenicity [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Development of an anti-CAR antibody response

  15. Minimal Residual Disease (MRD) [ Time Frame: Minimum of 2 years after bb2121 infusion ]
    Proportion of MRD evaluable subjects that are MRD negative

  16. Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Questionnaire will be used as a measure of health-related quality of life

  17. Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire [ Time Frame: Minimum 5 years after 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

  18. Subject-reported outcomes as measured by EORTC-QLQ-MY20 [ Time Frame: Minimum 5 years after bb2121 infusion ]
    Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality



Information from the National Library of Medicine

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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:

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. Subject has 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 and abnormal serum immunoglobulin kappa lambda free light chain ratio
  3. Subjects with one of the following cohort specific requirements:

    Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:

    • Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
    • Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
    • Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
    • Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
    • Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen

    Cohort 2 HR and with 1 prior anti-myeloma treatment regimen:

    • Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
    • Subject must have the following HR factors:

      • R-ISS stage III (see Appendix G) AND
      • Early relapse defined as:
      • For subjects that have undergone transplant, PD < 12 months since date of first transplant
      • For subjects that have received only induction, PD < 12 months since date of last treatment regimen which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone
  4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  5. Subject must have 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. Subject with known CNS involvement with myeloma
  2. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
  3. History or presence of clinically relevant central nervous system (CNS) pathology
  4. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
  5. Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
  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. Subject has received ASCT within 12 weeks prior to leukapheresis
  9. Subject has history of primary immunodeficiency
  10. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C
  11. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
  12. Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years
  13. Pregnant or lactating women
  14. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab

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): NCT03601078


Contacts
Contact: Rachelle Senzon rsenzon@celgene.com
Contact: Phyllis Whalen 908-897-4385 pwhalen@celgene.com

Locations
United States, Tennessee
Sarah Cannon Research Inst Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Celgene
Investigators
Study Director: Lars Sternas, MD, PhD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03601078     History of Changes
Other Study ID Numbers: BB2121-MM-002
U1111-1216-4209 ( Other Identifier: WHO )
2018-000264-28 ( EudraCT Number )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 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
bb2121
Relapsed and Refractory Multiple Myeloma
High Risk Multiple Myeloma

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