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

KARMMA-3

Overview

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard triplet regimens in subjects with relapsed and refractory multiple myeloma (MM). 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.

SparkCures ID 964
Trial Phase Phase 3
Enrollment 381 Patients
Treatments
Tags
Trial Sponsors
  • Celgene Corporation
NCT Identifier

NCT03651128

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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 must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  3. 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.
  4. 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
  5. Subject has received at least 2 but no greater than 4 prior MM regimens.
  6. Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.
  7. 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.
  8. Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
  9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  10. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.
  11. Adequate vascular access for leukapheresis
  12. Females of childbearing potential (FCBP) must:

    a. Have negative pregnancy test(s) as verified by the Investigator. This applies even if the subject practices true abstinence from heterosexual contact.

    b. Either practice true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption.

    c. Agree to abstain from breastfeeding during study participation. d. Refrain from tissue donation including egg cell donation or any other tissue/blood/organ donations.

  13. Male subjects must:

    a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, even if he has undergone a successful vasectomy.

    b. Refrain from tissue donation including sperm or any other tissue/blood/organ donations.

  14. Only subjects that would be considered for any of the 5 proposed standard regimens (DPd, DVd, IRd, Kd, or EPd), as judged by the investigator, should be included in the study.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. 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.
  3. Subject has any condition that confounds the ability to interpret data from the study.
  4. Subject has nonsecretory multiple myeloma (MM).
  5. 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)

  6. Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.
  7. 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
  8. Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis.
  9. Subject with known central nervous system (CNS) involvement with myeloma.
  10. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
  11. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
  12. Subject has a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
  13. Subject was treated with DARA in combination with POM with or without dex (DP±d) as part of their most recent anti-myeloma treatment regimen, cannot receive DPd as bridging therapy but may receive DVd, IRd, Kd or EPdas bridging as per Investigator's discretion if randomized to Treatment Arm A.
  14. Subject was treated with DP±d as part of their most recent anti-myeloma treatment regimen, cannot receive DPd if randomized to Treatment Arm B but may receive DVd, IRd, Kd, or EPd as per Investigator's discretion.
  15. Subject was treated with DARA in combination with BTZ with or without dexamethasone (DV±d) as part of their most recent anti-myeloma treatment regimen, cannot receive DVd as bridging therapy but may receive DPd, IRd, Kd, or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
  16. Subject was treated with DV±d as part of their most recent anti-myeloma treatment regimen, cannot receive DVd if randomized to Treatment Arm B but may receive DPd, IRd, Kd, or EPd as per Investigator's discretion.
  17. Subject was treated with IXA in combination with LEN with or without dexamethasone (IR±d) as part of their most recent anti-myeloma treatment regimen, cannot receive IRd as bridging therapy but may receive DPd, DVd, Kd, or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
  18. Subject was treated with IR±d as part of their most recent anti-myeloma treatment regimen, cannot receive IRd if randomized to Treatment Arm B but may receive DPd, DVd, Kd, or EPd as per Investigator's discretion.
  19. Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy.
  20. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization.
  21. Subject has received any of the following within the last 14 days prior to randomization:

    a. Plasmapheresis b. Major surgery (as defined by the Investigator) c. Radiation therapy other than local therapy for myeloma-associated bone lesions d. Use of any investigational agents and systemic anti-myeloma drug therapy

  22. Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection fraction (LVEF) < 45%.
  23. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed.
  24. Subject is positive for human immunodeficiency virus (HIV-1 and HIV-2), chronic or active hepatitis B or active hepatitis A or C.
  25. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management.
  26. Subject has 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 randomization.
  27. Hypersensitivity to DARA, thalidomide, lenalidomide, POM, BTZ, IXA, CFZ, ELO or dexamathasone. This includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy.
  28. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab or hypersensitivity to the excipients contained in the formulation of DARA, POM, LEN, IXA, BTZ, CFZ, ELO or dexamethasone.
  29. Subject is a female who is pregnant, nursing, or breastfeeding
  30. For a subject randomized to Treatment Arm B and will be on a POM- or LEN-containing regimen; unable or unwilling to undergo protocol required thromboembolism prophylaxis.
  31. Subject is intolerant to bortezomib, or has acute diffuse infiltrative pulmonary and pericardial disease, subject cannot receive DVd as bridging therapy if randomized to Treatment Arm A or cannot receive DVd if randomized to Treatment Arm B.
  32. Subject was treated with K±d as part of their most recent anti-myeloma treatment regimen, cannot receive Kd if randomized to Treatment Arm B but may receive DPd, DVd, IRd or EPd as per Investigator's discretion.
  33. Subject was treated with EP±d as part of their most recent anti-myeloma treatment regimen, cannot receive EPd if randomized to Treatment Arm B but may receive DPd, DVd, Kd or IRd as per Investigator's discretion.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Verified Winship Cancer Institute of Emory University
Verified Memorial Sloan Kettering Cancer Center
Verified John Theurer Cancer Center Hackensack Meridian Health

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NewYork-Presbyterian/ Weill Cornell Medical Center

New York, NY

Northwestern University Feinberg School of Medicine

Chicago, IL

Blood and Marrow Transplant Group of Georgia

Atlanta, GA

Mayo Clinic (Jacksonville)

Jacksonville, FL

University of Colorado Cancer Center Anschutz Cancer Pavilion

Aurora, CO

UCLA Medical Center, Santa Monica UCLA Health

Santa Monica, CA

Mayo Clinic (Rochester)

Rochester, MN

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Alabama
Arizona
California
UCLA Medical Center, Santa Monica UCLA Health

Santa Monica, CA

Colorado
University of Colorado Cancer Center Anschutz Cancer Pavilion

Aurora, CO

Florida
Mayo Clinic (Jacksonville)

Jacksonville, FL

Georgia
Verified Winship Cancer Institute of Emory University

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Blood and Marrow Transplant Group of Georgia

Atlanta, GA

Illinois
Northwestern University Feinberg School of Medicine

Chicago, IL

Indiana
Kansas
Maryland
Massachusetts
Michigan
Minnesota
Mayo Clinic (Rochester)

Rochester, MN

Missouri
Verified Alvin J. Siteman Cancer Center Washington University Medical Campus

SparkCures Verified Accurate, up-to-date information. Learn more

New Jersey
Verified John Theurer Cancer Center Hackensack Meridian Health

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New York
Verified Memorial Sloan Kettering Cancer Center

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NewYork-Presbyterian/ Weill Cornell Medical Center

New York, NY

North Carolina
Pennsylvania
Tennessee
Texas
Utah
Washington
Wisconsin
Verified UW Carbone Cancer Center University of Wisconsin Health

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International Locations

This trial has active trial locations in countries outside of the United States.

Our system currently only provides clinical trial matching services for myeloma patients in the United States.

You can view this clinical trial's international locations by visiting ClinicalTrials.gov. Please be aware that the government website may include information that is inaccurate and/or out-of-date.

Resources

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