A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma

Study Overview
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Brief Summary
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This is a single-center, non-randomized study to evaluate the safety and efficacy of C-CAR088 in relapsed or refractory multiple myeloma patients.

Detailed Description
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The study will include the following sequential phases: Screening, Apheresis, Baseline, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up Visit.

Official Title
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A Phase # Study Evaluating Safety and Efficacy of C-CAR088 Treatment in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: C-CAR088


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years old, male or female; The patient volunteered to participate in the study, and he or his legal guardian signed the Informed Consent; Patients with a clear diagnosis of relapsed or refractory multiple myeloma 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 Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination; At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy. ECOG scores 0 - 1; Good cardiac and pulmonary organ function; Expected survival time > 12 weeks;. 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: Have a history of allergy to cellular products; Laboratory testing occurs when: including but not limited to, serum total bilirubin ≥1.5mg / dl; serum ALT or AST is 2.5 times higher than the upper limit of normal value; serum creatinine ≥2.0mg / dl; hemoglobin <80g / L; absolute neutrophil count <1000 / mm3 or dependent on GCSF or Other growth factors can maintain the centriole count ≥1000 / mm²; platelet count <50000 / mm³ or the above level can be maintained due to platelet transfusion; 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; A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease; Need to use any anticoagulant (except aspirin); Patients requiring urgent treatment due to tumor progression or spinal cord compression; Patients with CNS metastasis or symptoms of CNS involvement; After allogeneic hematopoietic stem cell transplantation; Plasma cell leukemia; Patients with autoimmune diseases, immunodeficiency, or other immunosuppressive agents; Uncontrolled active infection; Have used any CAR T cell products or other genetically modified T cell therapy before; 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; Have a history of alcoholism, drug addiction and mental illness; Participated in any other clinical trial within 1 months; The investigators believe that there are other circumstances that are not suitable for the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C-CAR088<br>Lymphocytes will be transduced with lentiviral vector containing CAR-BCMA gene | Drug: C-CAR088<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of adverse events (TEAEs) within 30 days after intravenous infusion of C-CAR088 |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | ORR(including sCR / CR / VGPR / PR, based on IMWG 2016 efficacy evaluation criteria) | 12 months | 
| Progression free survival (PFS) | PFS(based on IMWG 2016 efficacy evaluation criteria) | 6 months#12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma