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

May 15, 2026 updated by: Fred Hutchinson Cancer Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

This is a dose-escalation study of 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 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.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: FHCC Immunotherapy Intake
  • Phone Number: 855-557-0555

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch/University of Washington Cancer Consortium
        • Contact:
        • Contact:
          • FHCC Immunotherapy Intake
          • Phone Number: 855-557-0555
        • Principal Investigator:
          • Elizabeth Krakow

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Biological: CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR
Given IV
Other Names:
  • CD8+ and CD4+ Donor Memory T-cells-expressing pRRLSIN iC9-HA1 TCR2-RQR-CD8
  • HA-1 TCR CD8+ and CD4+ Tm Cells
  • HA-1 TCR T Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells
Time Frame: Up to 12 weeks after T-cell infusion
Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Up to 12 weeks after T-cell infusion
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)
Proportion of subjects for whom a HA-1 TCR T cell product can be produced.
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)
Proportion of subjects for whom a HA-1 TCR T cell product can be administered.
At time of T cell infusion (at day 0)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood
Time Frame: Up to 1 year
Evaluated by tetramer and/or molecular tracking e.g. quantitative polymerase chain reaction (qPCR).
Up to 1 year
Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood
Time Frame: Up to 1 year
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow
Time Frame: Up to 1 year
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow
Time Frame: Up to 1 year
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Up to 1 year
Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells before adoptive T cell transfer
Time Frame: At the time of T cell infusion (at day 0)
Assessed by in vitro chromium release assay or equivalent cytotoxicity assay.
At the time of T cell infusion (at day 0)
Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells after adoptive T cell transfer
Time Frame: Up to 1 year
By in vitro chromium release assay or flow cytometric degranulation assay (CD107a) using samples of peripheral blood and/or bone marrow collected from subjects after adoptive T cell transfer.
Up to 1 year
Reduction of leukemia in the bone marrow in subjects who have measurable leukemia in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
Time Frame: Up to 1 year
Quantified by flow cytometry to determine percentage of leukemic cells in the marrow.
Up to 1 year
Reduction of recipient normal hematopoietic cells in the bone marrow in subjects who have measurable recipient normal hematopoietic cells in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
Time Frame: Up to 1 year
Quantified by variable number tandem repeat (VNTR) to determine percentage of normal recipient and donor cells in the marrow.
Up to 1 year
Proportion of subjects who develop new or recurrent symptoms or signs of graft-versus-host disease
Time Frame: Up to 1 year
Assessed using clinical evaluation and standard clinical graft versus host disease (GVHD) grading criteria
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

HighPass Bio, Inc.
PromiCell Therapeutics, Inc.

Investigators

  • Principal Investigator: Elizabeth Krakow, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2018

Primary Completion (Estimated)

October 16, 2027

Study Completion (Estimated)

July 16, 2028

Study Registration Dates

First Submitted

October 5, 2017

First Submitted That Met QC Criteria

October 25, 2017

First Posted (Actual)

October 31, 2017

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9716 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
  • NCI-2017-01054 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RG9217022 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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