BCMA Chimeric Antigen Receptor Expressing T Cells in Multiple Myeloma

Recruitment & Eligibility

Inclusion Criteria

Expected survival > 12 weeks
Diagnosis of Multiple Myeloma by MWG criteria 20
Patients previously received at least 3 different prior treatment regimens for multiple myeloma, including alkylating agent, protein inhibitors, and immunomodulator, and have disease progression in the past 60 days
Important organs function enough to tolerate this therapy
At least 90 days after stem cell transplantation
Clinical performance status of ECOG score 0-4
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
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
Suffering severe cardiovascular or respiratory disease
Poorly controlled hypertension
Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment
A history of mental illness and poorly controlled
Screening showing target cell transduction efficacy is lower than 30%, or T cell proliferation is not enough for infusion (less than 5 fold)
Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy
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
Active systemic infections or uncontrolled infection within 14 days prior enrollment
Subjects suffering disease affects the understanding of informed consent or complying with study protocol

Study & Design

Arm && Interventions

Group	Intervention	Description
anti-BCMA CAR-T	Fludarabine	Administration of anti-BCMA:TCRζ-4-1-BB CAR-T cells to patients with multiple myeloma
anti-BCMA CAR-T	Anti-BCMA CAR-T cells	Administration of anti-BCMA:TCRζ-4-1-BB CAR-T cells to patients with multiple myeloma
anti-BCMA CAR-T	Cyclophosphamide	Administration of anti-BCMA:TCRζ-4-1-BB CAR-T cells to patients with multiple myeloma

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
Duration of CAR-positive T cells in circulation	6 months	Duration of CAR-positive T cells in circulation
Total number of CAR-positive T cells infiltrated into lymphoma tissue	6 months	Total number of CAR-positive T cells infiltrated into lymphoma tissue
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm	8 weeks	Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm

Recruitment & Eligibility