CAR-T Cells in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study is aimed to evaluate the safety, feasibility and efficacy of CAR-T cell therapy in the treatment of relapsed or refractory multiple myeloma

Detailed Description
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This is a study to evaluate the safety, feasibility and efficacy of CAR-T cell therapy in the treatment of relapsed or refractory multiple myeloma. The Main research objectives: To evaluate the safety and efficacy of CAR-T cell therapy in patients with relapsed or refractory multiple myeloma. The Secondary research objectives: To evaluate the safety and efficacy of CAR-T cell therapy in patients with relapsed or refractory multiple myeloma.

Official Title
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An Open, Uncontrolled, Multicenter Clinical Trial to Explore the Safety, Efficacy, and Remission Phase of Chimeric Antigen Receptor T Cell (CAR-T) in the Treatment of Relapsed Refractory (R/R) Multiple Myeloma (MM)

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: BCMA CAR-T
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects voluntarily participated in the study and signed the informed consent form by themselves or their legal guardian; According to the international standard for multiple myeloma (IMWG 2014); Diagnosed as relapsed or refractory multiple myeloma. Relapsed and refractory were defined as follow. Relapsed: patients had received for at least 3 drugs with different mechanisms of action (including protease inhibitors and immunomodulators) and disease progression within 60 days of the most recent treatment. Refractory was defined as: disease progression occurred during the recent treatment, or disease progression occurred within 60 days after treatment; The expression of BCMA in myeloma cells was reported as positive by flow cytometry or immunohistochemistry; No antibody drug was administered within last 2 weeks before cell therapy; ECOG Scores: 0 1 Echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥ 50%, no serious arrhythmia; The subjects had no pulmonary infection, normal pulmonary function, and indoor air oxygen saturation ≥92%; There was no contraindication for peripheral blood sampling; The estimated survival time was more than 12 weeks; The urine pregnancy test of female subjects of childbearing age should be negative and not in lactation; the female or male subjects of childbearing age should take effective contraceptive measures during the whole research process. Exclusion Criteria: Have a history of allergy to any component of cell products; There are clinically significant cardiovascular diseases, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or any grade 3 (moderate) or grade 4 (severe) heart disease with cardiac function (according to the functional classification method of the New York Heart AssociationNYHA) with a history of myocardial infarction, angioplasty or stent implantation, unstable angina or other clinically significant heart disease within 12 months before admission; who has suffered from brain injury, consciousness disorder, epilepsy, more serious cerebral ischemia or cerebral hemorrhage disease; Patients who need urgent treatment due to tumor progression or spinal cord compression; The investigator determines that there are serious complications or diseases that will increase the risk of the subject or affect the study, including but not limited to, for example, cirrhosis, recent major trauma, etc; After allogeneic hematopoietic stem cell transplantation; Patients with autoimmune diseases, immunodeficiency or other diseases requiring immunosuppressive（excluding glucocorticoid）therapy; There was uncontrolled active infection; There were live vaccinations within 4 weeks before admission; Active hepatitis (positive for HBVDNA or HCVRNA), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to those with HIV infection; Subjects had a history of alcohol, drug or mental illness; The researchers believe that there are other conditions that subjects are not suitable to participate in this study.

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: volunteers<br>The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) Multiple Myeloma (MM) | Drug: BCMA CAR-T<br>* Volunteers will be treated with BCMA CAR-T cells<br>* Other names: senl_BCMA;Drug: Fludarabine<br>* 25mg/㎡ for D-4、D-3 and D-2<br>* Other names: flu;Drug: Cyclophosphamide<br>* 500mg/㎡ for D-3 and D-2<br>* Other names: ctx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Severe/Adverse Events as a Measure of Safety | Number of Participants with Severe/Adverse Events as a Measure of Safety | 28 days | 
| CAR-T Cell expansion level | Copies numbers of CAR in peripheral blood(PB) and/or bone marrow(BM) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of complete remission and partial remission | Objective response rate of complete remission and partial remission | 24 months | 
| Overall survival time | Overall survival time | 24 months |