Multiple Myeloma
Conditions
Keywords
Multiple Myeloma
Brief summary
This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR088 in relapsed or refractory multiple myeloma patient.
Detailed description
The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up.
Interventions
DRUGC-CAR088
Autologous BCMA-directed CAR-T cells, single infusion intravenously at a target dose of 1.0-9.0 x 10\^6 anti-BCMA CAR+T cells/kg. Other Name: CBM.BCMA Chimeric Antigen Receptor T cell.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old, male or female; 2. The patient volunteered to participate in the study, and he or his legal guardian signed the Informed Consent; 3. Meet the internationally accepted Criteria for the diagnosis of multiple myeloma (IMWG diagnostic criteria 2014); 4. Patients with a clear diagnosis of relapsed or refractory multiple myeloma； 5. The patient have one or more measurable multiple myeloma lesion, must include one of the following conditions: * Serum M protein≥1.0 g/dL(10g/L) * Urine M protein≥200 mg/24h * Serum free light chain(sFLC): κ/λ FLC ratio is abnormal and affected FLC ≥10mg / dL 6. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination; 7. ECOG scores 0 - 1; 8. Echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no severe arrhythmia; 9. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air. 10. Absolute neutrophil count ≥1.0 × 109 / L, platelet count ≥50 × 109 / L; total serum bilirubin ≤1.5mg / dl; serum ALT or AST less than 2.5 times the upper limit of normal; serum creatinine ≤2.0mg / dl; 11. No contraindications of peripheral blood apheresis; 12. Expected survival time \> 12 weeks;. 13. Female subjects of childbearing age must have a negative urine / blood pregnancy test within 7 days before cell therapy and not be in lactation; female or male subjects of childbearing age need to take effective contraception throughout the study.
Exclusion criteria
1. Have a history of allergy to cellular products; 2. Presence of clinically significant cardiovascular disease; 3. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease; 4. Need to use any anticoagulant (except aspirin); 5. Patients requiring urgent treatment due to tumor progression or spinal cord compression; 6. Patients with CNS metastasis or symptoms of CNS involvement; 7. After allogeneic hematopoietic stem cell transplantation; 8. Plasma cell leukemia; 9. Received systemic anti-tumor treatment within 2 weeks before apheresis, and within 1 week before apheresis, prednisone (or equivalent amount of other corticosteroids) was applied in excess of 5 mg/d ; 10. Patients with autoimmune diseases, immunodeficiency, or other immunosuppressive agents; 11. Uncontrolled active infection; 12. Have used any CAR T cell products or other genetically modified T cell therapy before; 13. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV infected persons; 14. Have a history of alcoholism, drug addiction and mental illness; 15. Participated in any other clinical trial within 1 months; 16. The investigators believe that there are other circumstances that are not suitable for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: The incidence of treatment-emergent adverse events (TEAEs) | 30 days | The incidence of treatment-emergent adverse events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 12 months | ORR(including sCR / CR / VGPR / PR, based on IMWG 2016 efficacy evaluation criteria) |
| Progression free survival (PFS) | 6 months、12 months | PFS(based on IMWG 2016 efficacy evaluation criteria) |
| The CART cell duration in vivo | 12 months | The copys of BCMA-CART DNA in peripheral blood with qPCR method |
| The soluble BCMA changes in peripheral blood | 12 months | The amount of soluble BCMA in peripheral blood with ELISA method |
Countries
China
Outcome results
None listed