HA-1 TCR T cell therapy for leukemia that returned or didn't respond after a donor stem cell transplant

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 1 dose-escalation trial delivering gene-modified CD4+ and CD8+ donor T cells that express an HA-1–specific T cell receptor to patients with relapsed or refractory acute leukemia after allogeneic hematopoietic cell transplant. Participants receive lymphodepleting chemotherapy (for example fludarabine and cyclophosphamide) 2–14 days before an intravenous infusion of the HA-1 TCR T cells, with doses escalated to define safety and the recommended dose. The protocol includes bone marrow and biospecimen collection and close monitoring for toxicity and response, with follow-up visits during the first 12 weeks and long-term follow-up out to 15 years. Eligibility requires HLA-A*0201 expression, the HA-1(H) genotype, and an appropriate donor as specified in the protocol.

Why it matters

Who can join: the full rules

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

Where it's running

• Fred Hutch/University of Washington Cancer Consortium
  Seattle, Washington, United States Recruiting

Study contacts

• Principal investigator: Elizabeth Krakow — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: FHCC Immunotherapy Intake
• Email: immunotherapy@fredhutch.org
• Phone: 206-606-4668

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.