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Clinical Trial 19813

Cancer Type: Malignant Hematology
Interventions:Bortezomib; CC-4047 (Pomalidomide); CC-5013 (Lenalidomide); Daratumumab; Dexamethasone; Ixazomib (Ninlaro); Lenalidomide (Revlimid); PS-341 (Bortezomib); Pomalidomide; Velcade (Bortezomib); bb2121; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Rachid Baz

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

Summary

Objective

Primary Objective: Compare the efficacy of bb2121 to standard triplet regimens in subjects with RRMM as measured by progression-free survival (PFS) Secondary Objectives: Evaluate the safety of bb2121 compared to standard triplet regimens in subjects with RRMM Evaluate additional efficacy parameters of bb2121 compared to standard triplet regimens in subjects with RRMM including overall survival (OS) Characterize the expansion and persistence of chimeric antigen receptor (CAR) + T cells, in the peripheral blood by vector copy number (VCN) in subjects treated with bb2121 Evaluate the percentage of subjects who attain minimal residual disease (MRD)negative status by EuroFlow and next generation sequencing (NGS) Evaluate the impact of bb2121 compared to standard triplet regimens on the changes in health-related quality of life (HRQoL) Evaluate the impact of bb2121 on health utility values compared with standard triplet regimens

Inclusion Criteria

  • Participant is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Participant has documented diagnosis of MM and measurable disease, as defined per protocol.
  • Participant has received at least 2 but no greater than 4 prior MM regimens.
  • Participant has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.
  • Participant 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.
  • Participant achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.

  • Exclusion Criteria

  • Participant has nonsecretory multiple myeloma (MM).
  • Laboratory abnormalities outlined per protocol.
  • Inadequate pulmonary function defined as oxygen saturation (SaO2) > Prior history of malignancies, other than MM, unless the participant has been free of the disease for ≥ 5 years
  • Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis.
  • Known central nervous system (CNS) involvement with myeloma.
  • Clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
  • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
  • History or presence of clinically relevant CNS pathology.
  • Participant 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 or IRd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
  • Participant 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 or IRd as per Investigator's discretion.
  • Participant was treated with DARA in combination with BTZ with or without dex (DV±d) as part of their most recent anti-myeloma treatment regimen, cannot receive DVd as bridging therapy but may receive DPd or IRd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
  • Participant 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 or IRd as per Investigator's discretion.
  • Participant was treated with IXA in combination with LEN with or without dex (IR±d) as part of their most recent anti-myeloma treatment regimen, cannot receive IRd as bridging therapy but may receive DPd or DVd as bridging as per Investigator's discretion if randomized to Treatment Arm A.
  • Participant 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 or DVd as per Investigator's discretion.
  • 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.
  • Participant has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization.
  • Participant 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
  • Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection fraction (LVEF) > Positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C.
  • 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.
  • 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 DARA, thalidomide, lenalidomide, POM, BTZ, IXA or dex. This includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy.
  • Additional exclusions apply