BCMA Chimeric Antigen Receptor Expressing T Cells in Multiple Myeloma

A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Subjects With BCMA-positive Multiple Myeloma

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.

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