Status:
RECRUITING
Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma
Lead Sponsor:
Sheba Medical Center
Conditions:
Multiple Myeloma
Relapse Multiple Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is an open label, abbreviated (3+3) dose escalation study in subjects with RRMM, followed by an extension phase at the selected safe dose. The dose escalation stage will involve recruitment of 3 ...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
September 19 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2028
Estimated Enrollment :
75 Patients enrolled
Trial Details
Trial ID
NCT05243212
Start Date
September 19 2021
End Date
September 1 2028
Last Update
January 31 2024
Active Locations (1)
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1
Chaim Sheba Medical Center, Tel Hashomer
Ramat Gan, Israel, 5262000