A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety of BB2121 in Subjects with High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in patients with HR (R-ISS Stage III per IMWG criteria) NDMM.
The primary objective of the study is to evaluate the safety and to determine the optimal dose of bb2121 in subjects with HR NDMM.
-Evaluate the efficacy of bb2121 in subjects with HR NDMM
-Evaluate feasibility of initiating lenalidomide maintenance therapy post-bb2121 infusion
-Characterize the expansion of chimeric antigen receptor (CAR) +T cells in the peripheral blood (cellular kinetics - pharmacokinetics [PK])
-Evaluate safety of lenalidomide maintenance therapy post-bb2121
-Evaluate MRD negative status by NGS
-Evaluate exploratory cytokines and chemokines associated with inflammatory cell activation and function before and after infusion of bb2121
-Evaluate biomarkers of disease and antigen burden (eg. BCMA expression in tumor, soluble (s)BCMA in blood) before and after infusion of bb2121
-Evaluate cell subtype and functional phenotypes of CAR T and endogenous immune cells before and after infusion of bb2121 in blood
-Evaluate genomic and transcriptomic characteristics of the tumor before and after bb2121 infusion
-Evaluate mechanisms of tumor sensitivity/resistance to bb2121 CAR T cell therapy
-Evaluate different MM potential prognostic subgroups by assessing genomic characteristics of tumor tissue (eg, TP53 mutation)
-Evaluate the immunogenicity of bb2121
Newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
18 years of age or older at the time of initial diagnosis of MM
Has measurable disease at initial diagnosis by (a) M-protein and/or (b) Light chain MM without measurable disease in the serum or urine
Has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG: (a) ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or; (b) ISS Stage III and serum LDH > ULN
Eastern Cooperative Oncology Group performance ≤ 1
Has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment: Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd) Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)
Received any treatments for MM other than up to 3 cycles of induction therapy per protocol
Any of the following laboratory anomalies:
Absolute neutrophil count 13.5 mg/dL (> 3.4 mmol/L)
Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal
Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
INR or aPTT > 1.5 × ULN
History or presence of clinically significant CNS pathology
Has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
Has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
Has moderate or severe pulmonary hypertension
Has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
Has not recovered from induction therapy-related toxicities (non-hematologic) to > Has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment
Has cardiac conditions such as (a) Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction > Has Pulmonary conditions such as: a) known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.
(b) Inadequate pulmonary function defined as oxygen saturation > Patient needs ongoing treatment with chronic immunosuppressants
History of primary immunodeficiency
Patient is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C
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