HA-1 TCR T cell therapy for leukemia that returned or didn't respond after a donor stem cell transplant
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 1 study will test whether giving specially engineered donor T cells called HA-1 TCR T cells is safe and what dose works for people whose acute leukemia came back or didn't respond after a donor stem cell transplant.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | N/A to 80 Years |
| Sex | All |
| Sponsor | Fred Hutchinson Cancer Center Academic / other |
| Drugs / interventions | immunotherapy, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT03326921 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates are people of any age with relapsed or refractory acute leukemia after allogeneic transplant who are HLA-A*0201 positive, have the HA-1(H) genotype, and have an eligible donor meeting the protocol criteria.
Not a fit: Patients who lack HLA-A*0201 or the required HA-1 genotype, who do not have an eligible donor as specified, or whose disease biology is not driven by HA-1 expression are unlikely to benefit.
Why it matters
Potential benefit: If successful, this approach could provide a targeted immune therapy that clears residual leukemia cells and prolongs remission after transplant.
How similar studies have performed: Related donor-derived and TCR-engineered T cell approaches have shown proof-of-concept activity in post-transplant leukemia, but HA-1–specific TCR therapy is relatively novel and remains early-stage.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Seattle, Washington
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.