Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients

Inclusion Criteria:

1. Histologically confirmed acute myeloid leukemia
2. Refractory or relapsed AML which will include:

   1. Refractory disease will be defined as at least 1 prior treatment with no remission.
   2. Relapsed disease will be defined as 5% or more blasts in bone marrow seen after remission.
   3. Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.
3. White blood cell (WBC) count \< 10 x 109/L;

   a. Use of hydroxyurea, prior to Cycle 1 and during Cycles 1 and 2, is permitted to lower the WBC count in the peripheral blood.
4. Age \> 18 years.
5. Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockroft-Gault formula.
6. AST and ALT ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
7. Bilirubin ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

Exclusion Criteria:

1. Have acute promyelocytic leukemia (APL).
2. Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
3. Have received prior radiation to maximally tolerated levels to any critical normal organ.
4. Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
5. Clinically significant cardiac disease.
6. Active, uncontrolled serious infection.
7. Have other non-myeloid malignancy within 2 years of entry (with exceptions).
8. Psychiatric disorder that would preclude study participation
9. Previous solid organ transplant (prior treatment with SCT is allowed but not if patient as GVHD or is still receiving immunosuppression/GVHD therapy).