Anti-CD19/BCMA Bispecific CAR-T Cell Therapy for R/R MM

Study Overview
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Brief Summary
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The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/BCMA bispecific chimeric antigen receptors (CARs) T cell therapy for relapsed and refractory multiple myeloma.

Detailed Description
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Primary Objectives 1. To determine the feasibility ad safety of anti-CD19/BCMA CAR-T cells in treating patients with BCMA-positive multiple myeloma. Secondary Objectives To access the efficacy of anti-CD19/BCMA CAR-T cells in patients with multiple myeloma. To determine in vivo dynamics and persistency of anti-CD19/BCMA CAR-T cells.

Official Title
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Clinical Study of Anti-CD19/BCMA Bispecific Chimeric Antigen Receptors (CARs) T Cell Therapy for Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma in Relapse, Multiple Myeloma Progression

Intervention / Treatment
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* Biological: anti-CD19/BCMA CAR-T cells
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected survival > 12 weeks Diagnosis of Multiple Myeloma by IMWG updated criteria (2014) Pathology demonstrated that BCMA-poitive malignant plasma cells exited in bone marrow or plamacytoma Exited measurable lesions and in accordance with one of the following test indicators: serum M protein≥1 g/dl; urine M protein≥200 mg/24h; serum free light chain≥10 mg/dl; diagnosis of plasmacytoma by biopsy The criteria for relapsed and refractory multiple myeloma: patients previously received at least 3 different prior treatment regimens for multiple myeloma, including protein inhibitors (eg: Bortezomib), and immunomodulator (eg: Revlimid), and have disease progression in the past 60 days At least 90 days after stem cell transplantation Clinical performance status of ECOG score 0-2 Creatinine≤2.0 mg/dl Bilirubin≤2.0 mg/dl The ALT/AST value is lower than 2.5-fold of normal value Accessible to intravenous injection, and no white blood cell collection contraindications Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom 5mg/day dose of Prednisone or other equivalent steroid hormone drugs (eg: Dexamethasone) were not used for two weeks before apheresis and CAR-T infusion Able to understand and sign the Informed Consent Document. Exclusion Criteria: Patients with symptoms of central nervous system Patients with second malignancies in addition to multiple myeloma Active hepatitis B or C, HIV infections Any other active diseases could affect the enrollment of this trial Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment Patients with organ failure Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy A history of mental illness and poorly controlled Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion Patients who are accounted by researchers to be not appropriate for this test Subjects suffering disease affects the understanding of informed consent or complying with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: anti-CD19/BCMA CAR-T cells<br>Chemotherapy with a classic combination with fludarabine and cyclophosphamide; Administration with anti-CD19/BCMA CAR-T cells in the BCMA-positive multiple myeloma patients. | Biological: anti-CD19/BCMA CAR-T cells<br>* Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-BCMA CARs<br>Drug: Fludarabine<br>* 30mg/m2/d<br>Drug: Cyclophosphamide<br>* 300mg/m2/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall remission rate defined by the standard response criteria for myeloma for each arm | Overall remission rate defined by the standard response criteria for myeloma for each arm | 8 weeks | 
| Duration of CAR-positive T cells in circulation | Duration of CAR-positive T cells in circulation | 6 months |