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

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

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

Official Title
-----------------
Immunotherapy With BCMA CAR-T Cells in Treating Patients With Relapsed or Refractory Multiple Myeloma

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Biological: BCMA CAR-T


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCMA CAR-T cells<br>Patients will be treated with BCMA CAR-T cells | Biological: BCMA CAR-T<br>* Biological: BCMA CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after BCMA CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First month post CAR-T cells infusion | 
| Efficacy: Overall Remission Rate (ORR) | Overall Remission Rate (ORR) including partial remission and complete | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy:duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| Efficacy: progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of BCMA CAR- T cells in the genomes of PBMC by qPCR method and percentage of BCMA CAR- T cells measured by flow cytometry method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | First month post CAR-T cells infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BCMA，MM