CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD38. This is a phase 1/2 study designed to determine the safety of the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy.
1. PRIMARY OBJECTIVES: 1. To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma. 2. To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of CD38 CAR-T cells over time. 2. SECONDARY OBJECTIVES: 1. For patients with detectable disease, measure anti-tumor response due to specificity CD38 CAR-T cell infusions. 2. The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
1\) Biological: Specificity CD38 CAR-T Cells 2) Day 0: 1-5x10e6/kg total dose .3) Other: Laboratory Biomarker Analysis
Biotherapeutic Department and Hematology Department of Chinese PLA
Beijing, Beijing Municipality, China
RECRUITINGNumber of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Time frame: 24 weeks
MTD of specificity CD38 CAR-T cells
The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells.
Time frame: 4 weeks
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
Time frame: 24 weeks
Six-month Objective response rate of complete remission and partial remission
Time frame: 24 weeks
Six-month Overall survival
Time frame: 24 weeks
Six-month Progression free survival
Time frame: 24 weeks
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