This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of universal chimeric antigen receptor-modified AT19 cells in patients with relapsed or refractory hematological malignancies.
* Adoptive transfer of autologous anti-CD19 CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies, including CD19+ B-cell acute lymphoblastic leukemia(B-ALL), B-cell chronic lymphoblastic leukemia(B-CLL), and B-cell lymphoma. * However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. * Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients. * Cord blood derived T cells from healthy donor are the source for production of universal anti-CD19 CAR-modified AT19 cells. CRISPR/cas9 gene-editing technology has been used to knockout TCRs and HLA-I to avoid GvHD and transplant rejection. * AT19 cells have exhibited potent cytotoxicity in CD19+ tumor cells and can effectively eradicate CD19+ tumor cells in xenograft mice models, without showing GvHD. * This study aims to evaluate prelimary safety and efficacy of the universal AT19 cells in patients with relapsed/refractory B-ALL, B-CLL, and B-cell lymphoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 300 mg/kg on day -5, -4, and -3; CAR-NK-CD19 Cells on day 0.
Union Hospital, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGUnion Hospital, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGIncidence of Treatment-related Adverse Events
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: within 2 years after infusion
Overall response rate(ORR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Complete response rate(CRR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Progress-free survival(PFS) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: 2 years after infusion
Duration of Response(DOR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: 2 years after infusion
Overall survival(OS) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: 2 years after infusion
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