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
