Multi-CAR T Cell Therapy in the Treatment of Multiple Myeloma

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