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)

9716

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.

2018-02-23

2027-10-16

2028-07-16

Early phase I

24

Inclusion Criteria: * 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 Exclusion Criteria: * Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (PI) * Fertile patients unwilling to use contraception during and for 12 months after treatment * Patients with a life expectancy \< 3 months of enrollment from coexisting disease other than leukemia * Patients who develop grade IV acute GVHD or severe chronic GVHD following most recent transplant prior to enrollment on the protocol * The presence of organ toxicities will not necessarily exclude patients from enrolling on the protocol at the discretion of the PI; however, a delay in the infusion of HA-1 TCR T cells may be required DONOR SELECTION EXCLUSION * Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection * Unrelated donor residing outside of the United States of America (USA) unless the donor screening, testing and leukapheresis occur at an NMDP-affiliated and qualified donor center and are facilitated by the NMDP.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ESTIMATED'}}

2024-03-21