FH-WT1-E50 TCR T Cells With Azacitidine for the Treatment of Minimal Residual Disease Positive Acute Myeloid Leukemia
Phase I Study of Autologous CD4+ and CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Treatment of MRD-Positive AML
4 other identifiers
interventional
9
1 country
1
Brief Summary
This phase I trial tests the safety, side effects and best dose of FH-WT1-E50 TCR T cells with azacitidine for the treatment of minimal residual disease (MRD) positive acute myeloid leukemia (AML). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize WT1, a protein on the surface of cancer cells. These WT1-specific T cells may help the body's immune system identify and kill WT1 cancer cells. Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving FH-WT1-E50 TCR T Cells with azacitidine may be safe and/or effective for the treatment of MRD positive AML.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 9, 2026
CompletedFirst Posted
Study publicly available on registry
June 12, 2026
CompletedStudy Start
First participant enrolled
October 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 19, 2030
Study Completion
Last participant's last visit for all outcomes
July 19, 2030
June 12, 2026
June 1, 2026
3.8 years
June 9, 2026
June 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of treatment related grade 3 or higher adverse events
From first infusion up to 1 year
Incidence of dose limiting toxicity
From first T cell infusion, up to 28 days
Secondary Outcomes (2)
Ability to reproducibly generate and infuse T cells at the planned dose level (feasibility)
From baseline up to 1 year after eligibility determination
Relapse
At 1 and 2 years after first infusion
Study Arms (1)
Treatment (FH-WT1-E50 TCR T cells, azacitidine)
EXPERIMENTALPatients undergo leukapheresis. 4 weeks later patients receive azacitidine IV. At least 4 weeks after the first azacitidine infusion, patients receive azacitidine IV followed by FH-WT1-E50 TCR T cells IV. If additional cells are available patients may receive a second infusion of azacitidine IV followed by FH-WT1-E50 TCR T cells IV, starting at 28 days, up to 1 year. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan/echocardiography and chest x-ray during screening and bone marrow biopsy and aspiration and blood sample collection throughout the study. Patients may undergo lumbar puncture on study and CT scan and/or PET scan throughout the study.
Interventions
Given IV
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo chest x-ray
Undergo CT scan
Undergo echocardiography
Undergo lumbar puncture
Undergo PET scan
Given MUGA scan
Given IV
Eligibility Criteria
You may qualify if:
- LEUKAPHERESIS: Age 18 years or older at the time of enrollment
- LEUKAPHERESIS: Confirmed diagnosis of AML that is not M3 subtype (acute promyelocytic leukemia \[APL\])
- LEUKAPHERESIS: Human leukocyte antigen (HLA) type HLA-A\*02:01 confirmed through HLA typing
- LEUKAPHERESIS: Tissue confirmation of WT1 expression by immunohistochemistry. Confirmation of diagnosis must be or have been performed by internal pathology review of archival biopsy material or other pathologic material at Fred Hutch/University of Washington Medical Center (UWMC)
- LEUKAPHERESIS: Capable of understanding and willing to provide informed consent
- LEUKAPHERESIS: Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last FH-WT1-E50 TCR T infusion
- LEUKAPHERESIS: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or Karnofsky Performance Status (KPS) ≥ 60%
- LEUKAPHERESIS: No immediate plan for allogeneic stem cell transplantation: patients must not have a planned allogeneic hematopoietic stem cell transplant (HCT) within 8 weeks of leukapheresis. Patients may still be considered for HCT in the future but must not have a scheduled transplant at the time of enrollment due to factors including, but not limited to, donor availability, performance status, comorbidities, or patient preference. Patients who subsequently become candidates for HCT (e.g., donor identified or improvement in performance status) may proceed to transplant at the discretion of the treating physician without a mandated waiting period related to study participation
- LEUKAPHERESIS: Creatinine clearance ≥ 30 ml/min by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or 24-hour urine clearance
- LEUKAPHERESIS: Total bilirubin \< 3.0 mg/dL. Participants with suspected Gilbert syndrome may be included if total bilirubin (tBili) \> 3mg/dL but no other evidence of hepatic dysfunction
- LEUKAPHERESIS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x upper limit of normal (ULN)
- LEUKAPHERESIS: Participants 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be ≥ 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
- START OF TREATMENT: Presence of Measurable Residual Disease (MRD) after chemotherapy at the time of screening. Patients must have achieved a morphologic remission (marrow that is at least 10% cellular with \< 5% blasts on morphologic review) with detectable MRD, regardless of incomplete recovery of neutrophil counts/less than 1,000/mm3 (CRi) or platelet counts less than 100,000/mm3 (CRp).
- MRD definition:
- MRD by flow cytometry: defined by any abnormal myeloid blasts identified by flow cytometric analysis.
- +8 more criteria
You may not qualify if:
- LEUKAPHERESIS: Prior solid organ transplant or allogeneic hematopoietic stem cell transplant. Kidney transplant participants will be considered on a case-by-case basis requiring discussion with principal investigator (PI). If the participant has had a kidney transplant, participant must have dialysis access, dialysis plan, supportive nephrologist, willingness to stop transplant immunosuppression, and express understanding that rejection is possible outcome. Dialysis or costs related to transplant kidney will not be supported by the study. Participants having had any other solid organ transplants will be excluded, as will those with any history of allogeneic hematopoietic stem cell transplant
- START OF TREATMENT: Evidence of TET2, ASXL1 or DNMT3a mutations as sole evidence of MRD
- START OF TREATMENT: Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the trial through 4 months after last T cell infusion. Participants of childbearing potential must have a negative serum pregnancy test within the 2 weeks (14 days) preceding T cell infusion. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)
- START OF TREATMENT: Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case-by-case exemptions are possible with approval by PI
- START OF TREATMENT: Unable to generate FH-WT1-E50 TCR T cells for infusions. However, if a lower than planned number of cells is available, the participant will have the option to receive the generated WT1-specific T cells
- START OF TREATMENT: Corticosteroid therapy at a systemic dose equivalent of \> 0.5 mg/kg of prednisone-equivalent per day. The following treatments are permitted: intranasal, inhaled, topical, or local steroid applications; systemic corticosteroids at physiologic doses equivalent to no more than 10 mg/day prednisone; steroids as premedication for contrast dye allergy
- START OF TREATMENT: Concurrent use of other investigational anti-cancer agents
- START OF TREATMENT: Active uncontrolled infection: HIV positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication
- START OF TREATMENT: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- START OF TREATMENT: Known allergic reactions to any of the components of study treatments
- START OF TREATMENT: Other medical, social, or psychiatric factors that interfere with medical appropriateness and/or ability to comply with study, as determined by the PI
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Francesco Mazziotta, MD, PhD
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
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
June 9, 2026
First Posted
June 12, 2026
Study Start (Estimated)
October 1, 2026
Primary Completion (Estimated)
July 19, 2030
Study Completion (Estimated)
July 19, 2030
Last Updated
June 12, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- IPD and supporting documents will become available after primary manuscript publication or within 12 months of study completion, whichever occurs later. Data will remain available for a period of at least 5 years following initial release. Access may begin after publication-related data lock and completion of required data de-identification and curation processes.
- Access Criteria
- Access to IPD and supporting materials will be granted to qualified researchers whose proposed use is consistent with scientifically sound secondary analyses. Requests will require submission of a research proposal, institutional affiliation, and IRB or ethics approval or exemption where applicable. Data will be shared under a data use agreement that prohibits re-identification attempts and restricts use to non-commercial research. Requests will be reviewed by a study steering committee or designated data access committee. Data will be shared via a controlled-access repository or secure data-sharing platform, with appropriate governance and security controls. A dedicated controlled-access data repository will be established upon study completion. The URL will be provided when the repository becomes active.
Individual participant data (IPD) that will be shared include de-identified clinical and laboratory data from enrolled Acute Myeloid Leukemia (AML) participants, including baseline demographics, clinical outcomes, treatment-related variables, adverse events, and all data underlying published results. In addition, multi-omic datasets will be shared, including single-cell RNA sequencing data, spatial transcriptomics data, and flow cytometry data generated from participant biospecimens. All shared data will be de-identified in accordance with applicable privacy regulations and institutional policies.