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Protocol No. UW18105

Principal Investigator Callander, Natalie

Phase III

Age Group Adult

Scope National

Sponsor Type Industry

Title A Phase 3, Multicenter, Randomized, Open Label Study to Compare the Efficacy and Safety of BB2121 Versus Standard Regimens in Subjects with Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)

Objective We want to find out if a CAR-T therapy called bb2121 is a better treatment for relapsed or refractory multiple myeloma than a standard triplet regimen. These standard regimens are:
  • Daratumumab in combination with pomalidomide and dexamethasone (DPd)
  • Daratumumab in combination with bortezomib and dexamethasone(DVd)
  • Ixazomib in combination with lenalidomide and dexamethasone(IRd)
    bb2121 is investigational. This means that the US Food and Drug Administration (FDA) has not approved bb2121 for the treatment of relapsed or refractory multiple myeloma, and bb2121 can only be given in a research study. The standard triplet regimens are approved by the FDA for the treatment of multiple myeloma

  • Treatment In this study you will be assigned by chance to get either the investigational therapy, bb2121, or one of the three standard triplet regimens
    If you are assigned to receive one of the standard triplet regimens, the study doctor will determine which regimen you will receive based on your prior anti-myeloma treatment regimens
    If you are assigned to the investigational therapy, some of your T cells (a kind of white blood cell, which form part of your body's immune system) will be collected from your blood in a procedure called leukapheresis. The collected cells will then be modified in a laboratory, so that they can recognize and destroy the multiple myeloma cells. After approximately 4 to 5 weeks, the modified T cells, now called bb2121 T cells, will be infused back into your blood

    Description Phase 3, Randomized, Open Label Study of BB2121 versus Standard Triplet Regimens in Subjects with Relapsed and Refractory Multiple Myeloma

    Key Eligibility
  • 18 years of age or older
  • Has documented diagnosis of Multiple Myeloma and measurable disease, as defined by the protocol
  • Has received at least 2 but no greater than 4 prior MM regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered as one regimen
  • Has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles
  • Must be refractory to the last treatment regimen
  • Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen
  • ECOG Performance status of 0-1
  • Adequate vascular access for leukapheresis
  • Can not be pregnant or breastfeeding
  • Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
    EXCLUSION
  • Has nonsecretory Multiple Myeloma
  • Has any laboratory abnormalities as defined by protocol
  • Has inadequate pulmonary function defined as oxygen saturation (SaO2) less than 92% on room air
  • Has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia,POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis
  • Known central nervous system (CNS) involvement with myeloma
  • Has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal
  • 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
  • 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
  • Has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization
  • Left ventricular ejection fraction (LVEF) less than 45%
  • Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose)
  • Positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C
  • Uncontrolled infection requiring IV therapy
  • 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
  • Hypersensitivity to any of the study treatment medications
  • 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
  • Subject is intolerant to bortezomib, subject cannot receive DVd as bridging therapy if randomized to Treatment Arm A or cannot receive DVd if randomized to Treatment Arm B
  • Prior treatment regimes have exclusion requirements please contact study coordinator for details

  • Applicable Disease Sites Multiple Myeloma

    Status Open

    Participating Institutions UW Hospital and Clinics