The aim of this clinical trial is to assess the feasibility, safety and efficacy of autologous CAR T cell immunotherapy targeting multiple cancer cell surface antigens in relapsed and refractory multiple myeloma patients. Another goal of the study is to learn more about the persistence and function of CAR T cells in the body.

Multiple myeloma (MM) is a malignancy of plasma cells, which remains a clinical challenge despite advanced therapeutic interventions including novel molecular therapies and stem cell transplantation (SCT). This trial is to test the safety and efficacy of T cells genetically modified to specifically target several MM surface antigens, including BCMA, CD38, CD56, CD138 or alternative MM surface antigens, based on a multi-CAR T cell immunotherapy approach. Another goal of the study is to investigate the persistence and function of CAR T cells in the body after CAR T cell infusion.

Inclusion Criteria:

• Male and female subjects with surface antigen confirmed multiple myeloma with no available curative treatment options (including autologous or allogeneic SCT).
• Complete remission (CR) cannot be achieved after at least 4 prior combination therapy regimens.
• MM in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid diseases, or lack of available donor.
• Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
• Relapsed after prior autologous or allogenic SCT MM patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
• Residual disease after primary therapy and not eligible for ASCT
• Expected survival > 12 weeks
• Creatinine < 2.5 mg/dl
• ALT (alanine aminotransferase)/AST (aspartate aminotransferase) < 3x normal
• Bilirubin < 2.0 mg/dl
• Any relapse after prior SCT is eligible regardless of other prior therapy
• Adequate venous access for apheresis, and no other contraindications for leukapheresis
• Voluntary informed consent is given

Exclusion Criteria:

• Pregnant or lactating women
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previous related CAR-T cell therapy Any uncontrolled active medical disorder that would preclude participation
• HIV infection