T Cells Expressing a Bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

This is an interventional treatment trial for CS1+ or BCMA+ Multiple Myeloma Read More

Inclusion Criteria:

Each potential subject must meet all of the following criteria to be enrolled in the study:

1. Aged 18-78 years old, males or females.
2. Relapsed or refractory multiple myeloma according to IMWG diagnostic criteria.
3. Received at least 2 prior lines of treatment for multiple myeloma, including a proteasome inhibitor and an immunomodulatory drug.
4. Detectable MM cells in bone marrow by conventional morphologic methods or flow cytometry, and positive expression of CS1 or BCMA on MM cells as confirmed by immunohistochemistry or flow cytometry.

5. Measurable diseases at screening as defined by any of the following:

   • Serum M-protein level ≥1.0g/dL;
   • Urine M-protein level ≥200mg/24 hours;
   • Serum immunoglobulin free light chain(FLC) ≥10 mg/dL provided abnormal FLC ratio.
6. Recovery to grade 1 or baseline of toxicities due to prior treatment, excluding hematologic toxicities and toxicity of no clinical significance, like alopecia.
7. ECOG Performance Status 0 ~ 2 (ECOG status of larger than 2 points caused by MM osteolytic destruction is accepted).

8. Good organ function at screening as defined by any of the following:

   • AST and ALT ≤ 2.5×upper limit of normal (ULN);
   • Total bilirubin≤ 2.0×ULN;
   • Creatinine clearance ≥30 mL/min/1.73m2;
   • Ejection fraction of heart ≥50%, and no clinically significant abnormal ECG findings.

9. Clinical laboratory values meeting the following criteria at screening:

   • Absolute Neutrophil Count(ANC) ≥1.0×10^9/L;
   • Platelets ≥30×10^9/L;
   • Absolute Lymphocyte Count ≥1.0×10^8/L;
   • Hemoglobin(Hb) ≥6.0g/dL.
10. Women of childbearing potential must have a negative pregnancy test at screening.
11. Patients with extramedullary lesions were eligible.
12. Patients who received prior allogeneic or autologous stem cell transplantation at least three months before screening were eligible.
13. Sign the informed consent voluntarily.

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study:

1. Evidence of serious viral, bacterial, or uncontrolled systemic fungal infection.
2. Seropositive for human immunodeficiency virus (HIV) antibody.
3. Seronegative for hepatitis B antigen or a known history of hepatitis B.
4. Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive) or a known history of hepatitis C.
5. Systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose within 2 weeks prior to apheresis.
6. Active autoimmune disease or a history of autoimmune disease within 3 years.
7. The following cardiac conditions: Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment; History of clinically significant ventricular arrhythmia or unexplained; New York Heart Association stage III or IV congestive heart failure.
8. A history of epilepsy or other central nervous system diseases or altered mental status.
9. Known life-threatening allergies, hypersensitivity, or intolerance to BM38 CAR T cells or relevant lymphodepleting regimens (cyclophosphamide and fludarabine).
10. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within one year after receiving study treatment.
11. Any uncontrolled diseases, other than multiple myeloma, that may lead to abnormal death.
12. Being participating in other intervention studies.
13. Other cases excluded by the Investigators.