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

NCT ID: NCT03326921

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-23

Study Completion Date

2028-07-16

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Juvenile Myelomonocytic Leukemia Recurrent Acute Biphenotypic Leukemia Recurrent Acute Undifferentiated Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Refractory Acute Lymphoblastic Leukemia Refractory Adult Acute Lymphoblastic Leukemia Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm Recurrent Myelodysplastic Syndrome Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory Myelodysplastic Syndrome Acute Undifferentiated Leukemia Mixed Phenotype Acute Leukemia Recurrent Chronic Myeloid Leukemia, BCR-ABL1 Positive Refractory Chronic Myeloid Leukemia, BCR-ABL1 Positive Recurrent Acute Lymphoblastic Leukemia Recurrent Acute Myeloid Leukemia Myelodysplastic Syndrome Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Acute Biphenotypic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Minimal Residual Disease Recurrent Chronic Myelomonocytic Leukemia Recurrent Mixed Phenotype Acute Leukemia Leukemia Chronic Myeloid Leukemia, BCR-ABL1 Positive

Keywords

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HA-1 TCR Immunotherapy Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

Given IV

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Interventions

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

Given IV

Intervention Type BIOLOGICAL

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Other Intervention Names

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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 Biological Sample Collection

Eligibility Criteria

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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
Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HighPass Bio, Inc.

UNKNOWN

Sponsor Role collaborator

PromiCell Therapeutics, Inc.

UNKNOWN

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elizabeth Krakow

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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FHCC Immunotherapy Intake

Role: CONTACT

Phone: 206-606-4668

Email: [email protected]

FHCC Immunotherapy Intake

Role: CONTACT

Phone: 855-557-0555

Facility Contacts

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FHCC Immunotherapy Intake

Role: primary

FHCC Immunotherapy Intake

Role: backup

References

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Krakow EF, Brault M, Summers C, Cunningham TM, Biernacki MA, Black RG, Woodward KB, Vartanian N, Kanaan SB, Yeh AC, Dossa RG, Bar M, Cassaday RD, Dahlberg A, Till BG, Denker AE, Yeung CCS, Gooley TA, Maloney DG, Riddell SR, Greenberg PD, Chapuis AG, Newell EW, Furlan SN, Bleakley M. HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Blood. 2024 Sep 5;144(10):1069-1082. doi: 10.1182/blood.2024024105.

Reference Type DERIVED
PMID: 38683966 (View on PubMed)

Other Identifiers

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NCI-2017-01054

Identifier Type: REGISTRY

Identifier Source: secondary_id

9716

Identifier Type: OTHER

Identifier Source: secondary_id

RG9217022

Identifier Type: OTHER

Identifier Source: secondary_id

9716

Identifier Type: -

Identifier Source: org_study_id