Overview
The aim of this study is to assess the feasibility, safety and efficacy of universal CAR T cells targeting multiple myeloma. Another goal of the study is to learn more about the persistence and function of the universal CAR T cells in the body.
Description
Multiple myeloma (MM) is a malignancy of the plasma cells, which remains a clinical challenge despite advanced therapeutic interventions including novel molecular therapies and stem cell transplantation (SCT).
CAR-T therapy has proven to be a revolutionary treatment for hematological malignancies, but its manufacture is still limited by the high cost, and a long preparation time that is not conducive to timely treatment of patients. In addition, many MM patients suffer from long-term bone marrow suppression caused by tumor growth or prolonged and intense chemotherapies, resulting in exhaustion, aging and functional defects of autologous T cells, which substantially affect the quality of CAR-T cells and the clinical efficacy. The universal CAR-T cells could overcome many of the above problems.
By using universal type of CAR-T cells, the product can be supplied off-the-shelf without being customized from individual patients. In addition, the immediate availability means that patients under severe bone marrow suppression may get a chance to be treated with CAR-T cells to achieve disease remission. In addition, those patients who suffer from long-term immunosuppression due to tumor microenvironment or myelosuppressive chemotherapy would have the option of treatment with the universal CAR-T cells.
The purpose of this study is to assess the feasibility, safety and efficacy of several 4SCAR designs including BCMA, CD138, CD38 and CD19-specific universal CAR-T products targeting MM. Another goal is to learn more about the function of these universal CAR T cells and their persistency in the patients.
Eligibility
Inclusion Criteria:
- Patients with confirmed multiple myeloma failed curative treatment options (including autologous or allogeneic SCT).
- Complete remission (CR) cannot be achieved after at least 2 prior therapy regimens.
- High risk MM in CR1 or CR2 and not eligible for SCT because of age or comorbid diseases.
- 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 with 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 signed
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