B Cell Leukemia Clinical Trial
Official title:
Phase I Study to Evaluate Treatment of Relapsed or Refractory Leukemia With Donor-derived HSCT Following Donor-derived CD19/22 Bispecific CAR-T Cells or CD19-directed CAR-T Cells
Allogenic hematopoietic stem cell transplant (Allo-HSCT) is routinely used for treatment of aggressive hematological malignancies. The biological foundation of allo-HSCT is the graft-versus-leukemia (GVL) effect, which is primarily mediated by donor T cells present in the graft and is able to eradicate malignant B cells either CD19+ or CD19-. Relapse following an allo-HSCT remains a major challenge in the treatment of B-ALL. 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. Co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT has the potential to combine the CAR-T cell mediated targeted elimination of CD19 expressing B cells with GVL effect, which could have clear advantages in reducing the risk of relapse and the evolution of CD19− escape variants or clonally related malignancies in other lineages. Therefore, a complete and durable tumor responses induced by this immunotherapy could be expected.
1. PRIMARY OBJECTIVES:
1. To evaluate the feasibility and safety of donor-derived HSCT following
donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells in
patients with relapsed or refractory leukemia.
2. To evaluate the duration of in vivo persistence of adoptively transferred CAR-T
cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor
(RT-PCR) and Flow cytometry(FCM) analysis of PB,BM will be used to detect and
quantify survival of infused allo-CAR-T cells over time.
3. To evaluate the donor chimerism after co-infusion of donor-derived CD19/22
bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT
2. SECONDARY OBJECTIVES:
1. For patients with detectable disease, measure anti-tumor response due to
co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T
cells and donor-derived-HSCT.
The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The
allo-HSCT will be infused on day 2.
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