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NCT03601078
Recruiting
July 26, 2018
September 1, 2021
Brief summary:
This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with MM having progressed within one 18 months of initial treatment including autologous stem cell transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with inadequate response post ASCT during initial treatment (Cohort 2c) Approximately 181 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 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently.
Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only.
| 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) |
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF) 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 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 subjects 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 AND Early relapse defined as: Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance. Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 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: Subject used any investigational agents within 14 days of leukapheresis Subject received any of the following within the last 14 days of leukapheresis: Plasmapheresis Major surgery (as defined by the investigator) Radiation therapy other than local therapy for myeloma associated bone lesions Use of any systemic anti-myeloma drug therapy Subject with known central nervous system involvement with myeloma Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation History or presence of clinically relevant central nervous system (CNS) pathology Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis 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 Ongoing treatment with chronic immunosuppressants 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 Subject has received ASCT within 12 weeks prior to leukapheresis Subject has history of primary immunodeficiency Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years Pregnant or lactating women Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
United States, Arizona
Mayo Clinic Arizona
Scottsdale
United States, California
UCSF Medical Center
San Francisco
United States, Florida
Moffitt Cancer Center
Tampa
United States, Georgia
Emory University
Atlanta
United States, Massachusetts
Massachusetts General Hospital
Boston
United States, Massachusetts
Dana Farber Cancer Institute
Boston
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston
United States, Missouri
Washington University
Saint Louis
United States, Nebraska
University of Nebraska
Omaha
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack
United States, New York
Mt Sinai Medical Center - NY
New York
United States, New York
Columbia University Medical Center / New York Presbyterian Hospital
New York
United States, New York
Memorial Sloan Kettering Cancer Center
New York
United States, North Carolina
Levine Cancer Institute
Charlotte
United States, Tennessee
Sarah Cannon Research Inst
Nashville
United States, Texas
University of Texas Southwestern Medical Center
Dallas
United States, Texas
MD Anderson Cancer Center The University of Texas
Houston
United States, Washington
Swedish Cancer Inst
Seattle
United States, Wisconsin
Froedtert Hospital BMT Medical College of Wisconsin
Milwaukee
France
CHU de Poitiers
Poitiers
Germany
Universitaetsklinkum Hamburg-Eppendorf
Hamburg
Germany
University Hospital Tuebingen, Department of Internal Medicine
Tuebingen
Germany
Universitatsklinikum Würzburg
Würzburg
Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi
Bologna
Spain
Clinica Universitaria de Navarra
Pamplona
Spain
Hospital Universitario de Salamanca
Salamanca
United Kingdom
King's College HospitalGKT School of Medicine
London
Celgene
Study Director: Lars Sternas, MD, PhD Celgene