Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma

Inclusion criteria

• Bone marrow plasma cells must be at least 10% of total bone marrow cells based on a bone marrow biopsy/aspiration performed within 30 days of the start of protocol treatment.
• Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria.
• Subjects must have measurable MM as defined by at least one of the criteria below.

One or more of these abnormalities defines measurable disease

• Serum M-protein equal or greater than 0.4 g/dl (10 g/l).
• Urine M-protein equal or greater than 200 mg/24 h.
• Serum free light chain (FLC) assay: involved FLC level greater or equal to10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal.
• A biopsy-proven plasmacytoma
• Patients must have received at least 3 prior treatment regimens for multiple myeloma.
• Greater than or equal to 18 years of age.
• Able to understand and sign the Informed Consent Document.
• Clinical performance status of ECOG 0-2
• Subjects of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
• Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
• Seronegative for HIV- 1, 2 antibody.
• Seronegative for hepatitis B surface antigen (HBsAg) or HBsAg positive with negative PCR for HBV nucleotides in blood. (Treatment to prevent HBV reactivation is standard in any case of seropositivity for HBV).
• Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
• Syphilis negative.
• Absolute neutrophil count greater than or equal to 500/mm3 without the support of filgrastim or other growth factors.
• Platelet count greater than or equal to 30,000/mm3 without transfusion support
• Hemoglobin greater than 8.0 g/dl.
• Less than 5% plasma cells in the peripheral blood leukocytes
• At least 14 days must have elapsed since any prior systemic therapy at the time the subject starts the cyclophosphamide and fludarabine conditioning regimen, and subjects' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
• Systemic anti-myeloma therapy including systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to the required leukapheresis, within 2 weeks prior to CAR T-cell infusion, and for 30 days after the CAR T cell infusion, unless required for treatment of toxicity or other medical need.
• Cardiac ejection fraction greater than or equal to 45% by echocardiography within 6 weeks of the start of the treatment protocol.

Exclusion criteria

• Subjects with second malignancies in addition to multiple myeloma are not eligible if the second malignancy has required treatment within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
• Women who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Active systemic infections (defined as infections causing fevers or requiring antimicrobial treatment), or other major uncontrolled medical illnesses.
• Active HBV and HCV infection which is identified by positive PCR to viral nucleotides in blood.
• Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) and direct bilirubin > 2 x ULN
• Inadequate renal function defined by serum creatinine clearance /estimated clearance of ≤ 20(ml/min).
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Subjects with CNS involvement.
• Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 15 days prior to leukapheresis for CAR T-cell manufacture, or is currently enrolled in an investigational study. However, prior therapy with belantamab mafotodin can be used.