Gilteritinib-Azacitidine-Venetoclax Combination Therapy in Patients With Relapsed/Refractory Leukemia

The goal of this clinical trial is to learn if gilteritinib-azacitidine-venetoclax combination drug therapy works to treat adults with FLT3-wt acute myeloid leukemia (AML). It will also learn about the safety and efficacy of this treatment. The main question this clinical trial aims to answer are: * Will adding gilteritinib to standard-of-care therapy azacitidine-venetoclax show be more effective in treating AML FLT3-wt patients who have previously been treated with azacitidine and/or venetoclax for their disease and have had their cancer come back (relapsed) or have stopped responding to treatment (refractory)? All participants in this trial will receive the combination therapy. Participants will be on repeated 28-day cycles, for a minimum of 2 cycles, while on the study Participants will: * Take the gilteritinib once daily, every day * Take azacitidine and venetoclax on days 1-7 of each cycle * Keep a daily dose diary of the days and times they have taken their treatments * Visit the clinic every 4 weeks for checkups and tests

Inclusion Criteria: Participants must meet all the following inclusion criteria to be eligible for participation in this trial. 1. Age ≥ 18 years old at the time of informed consent. 2. Pathologically confirmed diagnosis of AML previously treated with azacitidine and venetoclax that are azacitidine and venetoclax-refractory, defined as: 2a. Primary refractory: Defined as no complete remission (CR) or CR with incomplete recovery (CRi) following at least 2 cycles of azacitidine and venetoclax with AML blasts ≥5% in the bone marrow, or 2b. Relapsed: Defined as recurrence of AML blasts ≥5% in the bone marrow after a previous CR or CRi to azacitidine and venetoclax 3. Confirmed to be negative for FLT3- internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations on repeat clinical testing following their last line of therapy 4. Adequate functional status (ECOG ≤ 2) 5. Participant is willing to provide informed consent and comply with trial procedures 6. Participants of either biological sex must be able and willing to use Health-Canada approved effective contraception methods starting 2-weeks prior to trial treatment, throughout the trial, and for 6 months following the last dose of trial drugs 7. For participants of child-bearing potential (menstruation within \ 450ms that is not corrected on repeat electrocardiogram (ECG) testing 5. Active and untreated CNS leukemia 6. Active solid organ malignancy requiring treatment in the last 24 months, with the exception of: 6a. Treated nonmelanoma skin cancer 6b. Completely treated breast carcinoma that is considered cured 6c. Completely treated cervical carcinoma that is considered cured 6d. Localized breast or prostate cancer receiving androgen deprivation therapy 6e. A previously treated malignancy that is considered cured with minimal risk of recurrence 7. Extramedullary disease without concomitant marrow based disease (blasts ≤5%) 8. Uncontrolled, active infection or untreated hepatitis B, C, or HIV 9. Known allergy or intolerance to azacitidine, venetoclax, or gilteritinib 10. Any comorbidity that the investigator believes would be incompatible with safe receipt or therapy 11. Inability to comply with requirements of the trial protocol 12. Pregnancy or breastfeeding 13. Unable or unwilling to use Health Canada-approved highly effective methods of contraception (i.e., hormonal contraceptives, vasectomy, tubal ligation, or double-barrier method), or abstinence while on the trial and for at least 6 months following the last dose of trial drugs. Waivers to the exclusion criteria will NOT be allowed.