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

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
anti-CD19/BCMA CAR-T cells	anti-CD19/BCMA CAR-T cells	1. Chemotherapy with a classic combination with fludarabine and cyclophosphamide; 2. Administration with anti-CD19/BCMA CAR-T cells in the BCMA-positive multiple myeloma patients.
anti-CD19/BCMA CAR-T cells	Fludarabine	1. Chemotherapy with a classic combination with fludarabine and cyclophosphamide; 2. Administration with anti-CD19/BCMA CAR-T cells in the BCMA-positive multiple myeloma patients.
anti-CD19/BCMA CAR-T cells	Cyclophosphamide	1. Chemotherapy with a classic combination with fludarabine and cyclophosphamide; 2. Administration with anti-CD19/BCMA CAR-T cells in the BCMA-positive multiple myeloma patients.

Primary Outcome Measures

Name	Time	Method
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	6 months	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

Secondary Outcome Measures

Name	Time	Method
Overall remission rate defined by the standard response criteria for myeloma for each arm	8 weeks	Overall remission rate defined by the standard response criteria for myeloma for each arm
Duration of CAR-positive T cells in circulation	6 months	Duration of CAR-positive T cells in circulation

Recruitment & Eligibility