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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: Lumbar Puncture; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Bone Marrow Aspiration; Procedure: Chest Radiography; Drug: Azacitidine; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Drug: Autologous HLA-A*02:01-restricted CD4+/CD8+ Anti-WT1 TCR/CD8ab-expressing T-cells; Procedure: Multigated Acquisition Scan

Detailed Description

OUTLINE:

Patients undergo leukapheresis. 4 weeks later patients receive azacitidine intravenously (IV). At least 4 weeks after the first azacitidine infusion, patients receive azacitidine IV followed by Autologous HLA-A*02:01-restricted CD4+/CD8+ Anti-WT1 TCR/CD8ab-expressing T-cells (FHWT1-E50 TCR T) 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 multigated acquisition (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 computed tomography (CT) scan and/or positron emission tomography (PET) scan throughout the study.

After completion of study treatment, patients are followed up at day 1, 3, 7, 14, 21, 28, 56, 84, 168, 252 and 336 then every 6 months for years 1-5 the yearly until year 15.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Fred Hutch Immunotherapy Intake; Phone Number: 206-606-4668; Email: immunotherapy@fredhutch.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Fred Hutch Immunotherapy Intake; Phone Number: 206-606-4668; Email: immunotherapy@fredhutch.org
      • Principal Investigator: Francesco Mazziotta, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Leukapheresis:

• 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

Inclusion Criteria at Start of Treatment:

• 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.
    • Molecular measurable residual disease (MRD): for patients with NPM1-mutated disease, we will incorporate a clinically validated quantitative NPM1 MRD assay performed at Fred Hutch. For patients with FLT3-ITD-mutated disease, MRD assessment will include a clinically validated FLT3-ITD assay performed at Invivoscribe. These assays are routinely used in clinical practice and have established performance.
• START OF TREATMENT: Participants must be willing to undergo serial tumor biopsies and/or aspirates for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the second infusion (if applicable) (these windows may vary due to manufacturing or clinical reasons). Should there be no marrow tissue that is accessible, participants will still be considered for participation, at the discretion of the investigator. Similarly, should an investigator determine that a marrow assessment cannot be performed safely for clinical reasons, those may be cancelled or rescheduled. Participants must be at least two weeks or five half lives (for small molecules) from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents
• START OF TREATMENT: ECOG performance status of 0, 1, or 2 or Karnofsky Performance Status (KPS) ≥ 60%
• START OF TREATMENT: Creatinine clearance ≥ 30 ml/min by CKD-EPI or 24-hour urine clearance
• START OF TREATMENT: Total bilirubin < 3.0 mg/dL. Participants with suspected Gilbert syndrome may be included if tBili > 3mg/dL but no other evidence of hepatic dysfunction.
• START OF TREATMENT: 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: Participants with a history of chronic obstructive pulmonary disease (COPD), emphysema, or greater than 30 pack year smoking history should undergo pulmonary function tests (PFTs) and meet the following criteria:

  • Forced expiratory volume in 1 second (FEV1) ≥ 50% of predicted and carbon monoxide diffusing capacity (DLCO) (corrected) ≥ 40% of predicted will be eligible

Exclusion Criteria for Leukapheresis:

• 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

Exclusion Criteria at Start of Treatment:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (FH-WT1-E50 TCR T cells, azacitidine); Patients 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.

Procedure: Lumbar Puncture; Undergo lumbar puncture; Other Names: LP; Spinal Tap; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Bone Marrow Aspiration; Undergo bone marrow aspiration; Procedure: Chest Radiography; Undergo chest x-ray; Other Names: Chest X-ray; Drug: Azacitidine; Given IV; Other Names: 5 AZC; 5-AC; 5-Azacytidine; 5-AZC; Azacytidine; Azacytidine, 5-; Ladakamycin; Mylosar; U-18496; Vidaza; 5-Azacitidine; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Procedure: Echocardiography Test; Undergo echocardiography; Other Names: Echocardiography; EC; Drug: Autologous HLA-A*02:01-restricted CD4+/CD8+ Anti-WT1 TCR/CD8ab-expressing T-cells; Given IV; Other Names: Autologous HLA-A*02:01-restricted WT1-E50 TCR-CD8ab CD4+/CD8+ T Cells; Autologous WT1-specific HLA-A*02:01-restricted TCR/CD8ab CD4-/CD8-positive T-cells; FH-WT1-E50 TCR T; Procedure: Multigated Acquisition Scan; Given MUGA scan; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; RNV Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to reproducibly generate and infuse T cells at the planned dose level (feasibility)	No formal statistical considerations will be used to evaluate this endpoint beyond a simple estimate of the proportion along with its 95% confidence interval.	From baseline up to 1 year after eligibility determination
Relapse	Defined as with or without measurable tumor burden prior to T cell transfer, including patients who convert to minimal residual disease-negative status during consolidation.	At 1 and 2 years after first infusion

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Francesco Mazziotta, MD, PhD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 19, 2030
• Study Completion (Estimated): July 19, 2030

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Physical Phenomena; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Aza Compounds; Nucleosides; Ribonucleosides; Electromagnetic Phenomena; Magnetic Phenomena; Diagnostic Techniques, Neurological; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Azacitidine; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Spinal Puncture; X-Rays
• Other Study ID Numbers: RG1126017; 2P01CA018029 (U.S. NIH Grant/Contract); 21042 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2026-02251 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.

IPD Sharing 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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No