Status:

RECRUITING

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

Lead Sponsor:

Fred Hutchinson Cancer Center

Collaborating Sponsors:

HighPass Bio, Inc.

PromiCell Therapeutics, Inc.

Conditions:

Juvenile Myelomonocytic Leukemia

Recurrent Acute Biphenotypic Leukemia

Eligibility:

All Genders

Up to 80 years

Phase:

PHASE1

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 (recurr...

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 i...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

February 23 2018

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

July 16 2028

Estimated Enrollment :

24 Patients enrolled

Trial Details

Trial ID

NCT03326921

Start Date

February 23 2018

End Date

July 16 2028

Last Update

November 14 2025

Active Locations (1)

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1

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States, 98109