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

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.

OUTLINE:

This is a dose-escalation study of CD4+ and CD8+ HA-1 TCR T cells.

Patients receive lymphodepleting chemotherapy ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells intravenously (IV).

After completion of study treatment, patients are followed up closely for 12 weeks and then every 6 months for years 1-5, and every year for years 6-15.

Initial study activity was funded in part by HighPass Bio, Inc. Current study activity is funded in part by PromiCell Therapeutics, Inc.

Eligibility Criteria:
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.