bcma chimeric antigen receptor expressing t cells in multiple myeloma

Conditions: Multiple Myeloma

Summary: the goal of this clinical trial is to study the feasibility and efficacy of anti-b-cell maturation antigen (bcma) expressing t cells in treating patients with multiple myeloma.

primary objectives 1. to determine the feasibility ad safety of bcma car-t cells in treating patients with multiple myeloma. 2. to determine in vivo dynamics and persistency of bcma car-t cells. 3. to access the efficacy of bcma car-t cells in patients with multiple myeloma. secondary objectives 1. to assess the bone marrow and tumor migration of bcma car-t cells. 2. to investigate the tumor killing capability of bcma car-t cells in vitro 3. to investigate the possibility of host immune response to the mouse derived bcma scfv, and evaluate its correlation to car-t persistence. 4. to correlate the subsets and differentiation of bcma car-t cells to observed anti-tumor efficacy.

Eligibility criteria:
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