HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

• Status: Recruiting
• Trial end date: 2025-07-16
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Collaborators: Alex's Lemonade Stand Foundation; HighPass Bio, Inc.; National Cancer Institute (NCI); The Leukemia and Lymphoma Society
• Treatments: Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

Inclusion Criteria:

• Patient age 0-75 years at the time of enrollment. Initially only patients who are >= 16 years old will receive HA-1-TCR T cell infusions on the protocol. Younger patients may be screened, enrolled in the protocol and monitored for relapse but will not be eligible for infusion until at least one patient >=16 years old has been treated and discussed with the Food and Drug Administration (FDA)

• 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.