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

Status: Active

Description

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 (RRMM). 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.

Eligibility Criteria

Inclusion 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 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 3. Subject has received at least 2 but no greater than 4 prior MM regimens. 4. Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. 5. 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. 6. Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen. 7. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: 1. Subject has nonsecretory multiple myeloma (MM). 2. Subject has any of the following laboratory abnormalities: 1. Absolute neutrophil count (ANC) < 1,000/μL 2. 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) 3. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level) 4. Serum creatinine clearance (CrCl) < 45 mL/min 5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) 6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) 7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome 8. 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) 3. Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air. 4. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years 5. Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis. 6. Subject with known central nervous system (CNS) involvement with myeloma. 7. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation. 8. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. 9. Subject has a history or presence of clinically relevant CNS pathology. 10. 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 or IRd as bridging as per Investigator's discretion if randomized to Treatment Arm A. 11. 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 or IRd as per Investigator's discretion. 12. Subject 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. 13. 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 or IRd as per Investigator's discretion. 14. Subject 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. 15. 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 or DVd as per Investigator's discretion. 16. 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. 17. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization. 18. Subject has received any of the following within the last 14 days prior to randomization: 1. Plasmapheresis 2. Major surgery (as defined by the Investigator) 3. Radiation therapy other than local therapy for myeloma-associated bone lesions 4. Use of any investigational agents and systemic anti-myeloma drug therapy 19. Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection fraction (LVEF) < 45%. 21. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C. 22. 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. 23. 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. 24. Hypersensitivity to DARA, thalidomide, lenalidomide, POM, BTZ, IXA or dex. This includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy. 25. 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 or dex. 26. Subject is a female who is pregnant, nursing, or breastfeeding 27. 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. 28 Subject is intolerant to bortezomib, subject cannot receive DVd as bridging therapy if randomized.

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Approved
Contact: Vladimir Kustanovich
Phone: 310-206-5756
Email: VKustanovich@mednet.ucla.edu

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Florida

Tampa
Moffitt Cancer Center
Status: Active
Name Not Available

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Illinois

Chicago
Northwestern University
Status: Active
Name Not Available

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: Active
Contact: Keith Stanley Lozefski
Phone: 317-278-7173
Email: klozefsk@iu.edu

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New Jersey

Hackensack
Hackensack University Medical Center
Status: Active
Name Not Available

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Name Not Available
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Celgene

Trial IDs

Primary ID BB2121-MM-003
Secondary IDs NCI-2018-02057, U1111-1217-9988, 2018-001023-38
Clinicaltrials.gov ID NCT03651128