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

NCT03326921 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 9716NCI-2017-01054RG9217022
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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; 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

HA-1; TCR; Immunotherapy; Leukemia

Outcome Measures

Primary Outcomes (3)

• Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells

  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

  Proportion of subjects for whom a HA-1 TCR T cell product can be administered.

  At time of T cell infusion (at day 0)

• Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells

  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

Secondary Outcomes (9)

• Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood

  Up to 1 year

• Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood

  Up to 1 year

• Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow

  Up to 1 year

• Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow

  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

  At the time of T cell infusion (at day 0)

Study Arms (1)

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

EXPERIMENTAL

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.

Biological: CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

Interventions

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

Given IV

Also known as: 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

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

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

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

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

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

Eligibility Criteria

• Age: Up to 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• HighPass Bio, Inc.: collaborator
• PromiCell Therapeutics, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 38683966 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Juvenile; Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Blast Crisis; Blastic Plasmacytoid Dendritic Cell Neoplasm; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Neoplasm, Residual; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Elizabeth Krakow

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

FHCC Immunotherapy Intake

CONTACT

206-606-4668; immunotherapy@fredhutch.org

FHCC Immunotherapy Intake

CONTACT

855-557-0555

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 31, 2017
• Study Start: February 23, 2018
• Primary Completion (Estimated): October 16, 2027
• Study Completion (Estimated): July 16, 2028
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)