Recruiting
Phase 1

HA-1 TCR

Sponsor:

Fred Hutchinson Cancer Center

Code:

NCT03326921

Conditions

Juvenile Myelomonocytic Leukemia

Recurrent Acute Biphenotypic Leukemia

Recurrent Acute Undifferentiated Leukemia

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent Childhood Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Interventions

CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR

Bone Marrow Aspiration

Biospecimen Collection

Study Details

Brief 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.

Conditions

Juvenile Myelomonocytic Leukemia

Recurrent Acute Biphenotypic Leukemia

Recurrent Acute Undifferentiated Leukemia

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent Childhood Acute Myeloid Leukemia

Study ID

NCT03326921

Start date

Feb 23, 2018

Status verified date

May, 2026

Completion date

Jul 16, 2028

Anticipated

Primary completion date

Oct 16, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Subject age 0-80 years at the time of enrollment.
  • Subject must express HLA-A\*0201
  • Subject must have the HA-1(H) genotype (RS\_1801284: A/G, A/A)
  • Subject 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
  • Subjects 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)
  • Subjects 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 subjects younger than 18 years old
  • Subjects 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
  • Subjects 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 subjects with low performance status

DONOR SELECTION INCLUSION

  • Donor age >= 18 years
  • Donors must be able to give informed consent

Exclusion Criteria:

  • Medical or psychological conditions that would make the subject unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)
  • Fertile subjects unwilling to use contraception during and for 12 months after treatment
  • Subjects with a life expectancy of < 3 months of enrollment from coexisting disease other than leukemia
  • Subjects who have ongoing grade IV acute GVHD or severe chronic GVHD following most recent transplant. Exception: the principal investigator (PI) may make an exception on a case-by-case basis to include such a subject if there is doubt surrounding the GVHD diagnosis and/or sustained significant improvement in GVHD severity
  • The presence of organ toxicities will not necessarily exclude subjects 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 human immunodeficiency virus (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 National Marrow Donor Program (NMDP)-affiliated and qualified donor center and are facilitated by the NMDP

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (CD4+ and CD8+ HA-1 TCR T cells)

Patients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide or debulking regimens as specified in the protocol) ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells IV.

Interventions

CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR

Given IV

Bone Marrow Aspiration

Undergo bone marrow aspiration

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

  • Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells [ Time Frame: At time of T cell infusion (at day 0) ]
  • Feasibility of administering minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells [ Time Frame: At time of T cell infusion (at day 0) ]
  • Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells [ Time Frame: Up to 12 weeks after T-cell infusion ]

Central Contacts and Locations

Central contacts

FHCC Immunotherapy Intake

206-606-4668immunotherapy@fredhutch.org

FHCC Immunotherapy Intake

855-557-0555

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

FHCC Immunotherapy Intake

206-606-4668immunotherapy@fredhutch.org

FHCC Immunotherapy Intake

855-557-0555

Principal Investigator:

Elizabeth Krakow

More Information

Sponsor

Fred Hutchinson Cancer Center

Last update posted

May 18, 2026

Last verified

May, 2026

Keywords

  • HA-1
  • TCR
  • Immunotherapy
  • Leukemia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Fred Hutchinson Cancer Center on 2026-05-18.