Safety and Efficacy Evaluation of BCMA-CART for Treating Multiple Myeloma

Study Overview
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Brief Summary
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This trial aims to evaluate the safety and efficacy of BCMA-CART in treating patients with relapsed or refractory multiple myeloma.

Detailed Description
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BCMA(B-Cell maturation antigen) is a tumor antigen of multiple myeloma . Using a genetic engineering strategy to assemble an anti-BCMA CAR(chimeric antigen receptor) in autologous T cells will help these CART cells to recognize and kill BCMA-expressing MM tumor cells. This trial aims to evaluate the safety and anti-tumor efficacy of autologous BCMA-CART in treating relapsed or treatment refractory multiple myeloma.

Official Title
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Safety and Efficacy Evaluation of Autologous BCMA-CART for Treating Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: BCMA-CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have the capacity to give informed consent; Confirmed diagnosis of active MM as defined by NCCN and IMWG criteria; Have a diagnosis of BCMA+ multiple myeloma (MM), (≥ 5% BCMA+ in CD138+ plasma cells by flow cytometry obtained within 45 days of study enrollment); Refractory and relapsed MM patients after > 2 cycles of induction therapy,or,have relapsed or treatment refractory disease following autologous stem cell transplant (ASCT); ECOG score=0-2. Exclusion Criteria: Pregnant or nursing women; Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy; Active infection, HIV infection, syphilis serology reaction positive; Active hepatitis B, hepatitis C at the time of screening; Significant hepatic dysfunction as following, SGOT(serum glutamic-oxaloacetic transaminase)> 5 x upper limit of normal; bilirubin > 3.0 mg/dL; Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis serious mental disorder; With severe cardiac, liver, renal insufficiency, diabetes and other diseases; Participate in other clinical research in the past three months; previously treatment with any gene therapy products; Contraindication to cyclophosphamide or fludarabine chemotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Patients undergo leukapheresis to separate their lymphocytes, from which CART cells are produced. Patients will receive a conditioning therapy with cyclophosphamide and fludarabine before CART therapy. BCMA-CART cells will be injected intravenously (IV) into patients on day 0.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCMA-CART<br>Autologous T cells transduced to express anti-BCMA chimeric antigen receptor (CAR) | Biological: BCMA-CART<br>* After a conditioning therapy, each patient will receive a treatment of BCMA-CART originated from their own peripheral blood mononuclear cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Proportion of patients in whom a response among complete response or partial response, as defined by International Myeloma Working group(IMWG) response criteria , will be observed. | Up to 90 days after T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events as a Measure of Safety | Adverse events assessed according to NCI-CTCAE v4.03 criteria | Baseline up to 35 days | 
| Duration of persistence of BCMA-CART | BCMA-CART duration be assessed by FACS or QPCR | Baseline up to 1 year |