a study of bcma-directed car-t cells treatment in subjects with r/r multiple myeloma

Conditions: Multiple Myeloma

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.

the study will include the following sequential phases: screening, pre- treatment (cell product preparation, lymphodepleting chemotherapy), c-car088 infusion and follow-up.

Eligibility criteria:
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 who have received at least 3 lines of mm (contains proteasome inhibitors and immunomodulatory therapies that progress or relapse during the most recent treatment or after the end of treatment). note: the planned treatment plan for one or more cycles is "one-line treatment"; induction chemotherapy, stem cell transplantation, and maintenance treatment (if there is no disease progression between them), it is considered as a one-line treatment plan; 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 cell ular products; 2. presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or any heart function grade 3 (moderate) or grade 4 (severe) heart disease (according to the new york heart association function classification method: nyha); patients with a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina pectoris or other clinically significant heart disease within 12 months before enrollment; 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. live vaccination within 4 weeks before enrollment; 14. 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; 15. have a history of alcoholism, drug addiction and mental illness; 16. participated in any other clinical trial within 1 months; 17. the investigators believe that there are other circumstances that are not suitable for the trial.

Keywords: multiple myeloma