Principal Investigator:Munshi, Nikhil, C.
Site Investigator(s):Raje, Noopur,
This is a 2-part, non-randomized, open label, multi-site Phase 1 study. the study design
consists of 2 parts: Part A (Dose Escalation), in which the RP2D is determined, and Part B
(Expansion Cohorts), in which subjects are treated with the determined RP2D.
Following consent, enrolled subjects will undergo a leukapheresis procedure to collect
autologous mononuclear cells for manufacture of investigational drug product (bb2121).
Following manufacture of the drug product, subjects will receive lymphodepleting therapy with
fludarabine and cyclophosphamide prior to bb2121 infusion. All subjects who have received
bb2121 infusion will be followed for up to 60 months on CRB-401.
All subjects who complete the study, as well as those who withdraw from the study after
receiving bb2121 for reasons other than death or meeting the early termination criteria, will
be asked to continue to undergo long-term follow-up in a companion study for up to 15 years
after their last bb2121 infusion, with a focus on long-term safety and efficacy.
18 years of age at the time of signing informed consent
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Subjects must have measurable disease including at least one of the criteria below: Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study Part A: Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents
Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy
Subjects with known central nervous system disease
Inadequate hepatic function
Inadequate renal function
Inadequate bone marrow function
Presence of active infection within 72 hours
Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission
Subjects with a history of class III or IV congestive heart failure or non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 6 months
Known human immunodeficiency virus (HIV) positivity
Subjects who have plasma cell leukemia or clinically significant amyloidosis
Pregnant or lactating women