Phase I Study of Adoptive Immunotherapy With CD8+ and CD4+ Memory T Cells Transduced to Express an HA-1-Specific T Cell Receptor (TCR) for Children and Adults With Recurrent Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HCT)
This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.
• Patient age 0-75 years at the time of enrollment.
• Patients must express HLA-A\*0201
• Patients must have the HA-1(H) genotype (RS\_1801284: A/G, A/A)
• Patients must have an adult donor for HCT who is adequately HLA matched by institutional standards (includes HLA-matched related or unrelated donors, and HLA-mismatched family donors, including haploidentical donors) and is either:
‣ HLA-A\*0201 positive and HA-1(H) negative (RS\_1801284: G/G) or
⁃ HLA-A\*0201 negative
• Patients who are currently undergoing or who previously underwent allogeneic HCT for
‣ Acute myeloid leukemia (AML) of any subtype
⁃ Acute lymphoid leukemia (ALL) of any subtype
⁃ Mixed phenotype/undifferentiated/any other type of acute leukemia, including blastic plasmacytoid dendritic cell neoplasm
⁃ Chronic myeloid leukemia with a history of blast crisis and:
• With relapse or refractory disease (\>= 5% marrow blasts, or circulating blasts) at any time after HCT
∙ With persistent rising minimal residual disease (defined as detectable disease by morphology, flow cytometry, molecular or cytogenetic testing but \< 5% marrow blasts by morphology, no circulating blasts on \>= 2 of two consecutive tests), refractory or ineligible for treatment with tyrosine kinase inhibitors at any time after HCT
⁃ Myelodysplastic syndrome (MDS) of any subtype
⁃ Chronic myelomonocytic leukemia (CMML)
⁃ Juvenile myelomonocytic leukemia (JMML)
• Patients must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative; parent or legal representative will be asked to consent for patients younger than 18 years old
• Patients must agree to participate in long-term follow-up for up to 15 years if they are enrolled in the study and receive T cell infusion
• Patients who have relapsed or have MRD after HCT may receive other agents for treatment of disease and remain eligible for the protocol
• A specific performance status score is not required for enrolling on the protocol; a delay in infusion of the HA-1 TCR T cells may be required for patients with low performance status
⁃ DONOR SELECTION INCLUSION
• Donor age \>= 18 years
• Donors must be able to give informed consent
• Patients must have an adult donor for HCT who is adequately HLA matched by institutional standards (includes HLA-matched related or unrelated donors, and HLA-mismatched family donors, including haploidentical donors) and is either:
‣ HLA-A\*0201 positive and HA-1(H) negative (RS\_1801284: G/G) or
⁃ HLA-A\*0201 negative