Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113

Inclusion Criteria Subjects must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Ages 18 to 75 years at the time of consent. * ECOG Performance Status of 0-2 within 7 days prior to registration; see Appendix I. * Patients must have AML, as defined, that is relapsed or refractory. Prior therapy including chemotherapy, immunotherapy, biological or targeted therapy (e.g. FMS-like tyrosine kinase-3 (FLT3) inhibitors, other kinase inhibitors, azacitidine, ATRA) is allowed. * CD33 expression (by flow or IHC) in at least 20% of the leukemia blasts per local pathologist. * Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline. * Demonstrate adequate organ function as defined in the table in the protocol; all screening labs to be obtained within 28 days prior to registration. * Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months * Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of Gemtuzumab and males for at least 3 months after the last dose of Gemtuzumab. * As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study Exclusion Criteria Subjects meeting any of the criteria below may not participate in the study: * Patients with history of prior use of GO or Venetoclax NOTE: Starting with dose cohort 3, prior therapy with venetoclax is allowed, provided patients do not have evidence of p53 deletion or mutations. If the dose cohort is de-escalated to dose cohort 2 due to toxicity in cohort 3, prior exposure to venetoclax will continue to be allowed, provided patients do not have evidence of p53 deletion/mutations. * History of myeloproliferative neoplasm \[MPN\] including myelofibrosis, essential thrombocythemia, polycythemia vera, CML with or without BCR-ABL1 translocation, and AML with BCR-ABL1 translocation. * More than three lines of prior therapy. A line of therapy consists of ≥1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens (e.g., 3-6 cycles of initial therapy with bortezomib-dexamethasone \[VD\] followed by stem cell transplantation \[SCT\], consolidation, and lenalidomide maintenance is considered 1 line). * WBC \>25 × 109/L. Cytoreduction is required (hydroxyurea as per local standard of care). * Acute promyelocytic leukemia. * Unresolved ≥grade 2 clinically significant nonhematologic toxicities from prior anticancer therapy or unresolved disseminated intravascular coagulation ≥ grade 2 per CTCAE v5 criteria. * History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities), with curative intent. * Investigational drug within 4 weeks of study entry. * History of CHF requiring treatment, left ventricular ejection fraction ≤ 50%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix II), or chronic stable angina * Patients who are HIV positive. * Known CNS involvement with AML. * Previous hematopoietic stem cell transplant within 2 months. * Previous history of veno-occlusive disease/sinusoidal obstruction syndrome. * Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] may participate. * Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). * Patients who have received strong and/or moderate CYP3A inducers or inhibitors within 7 days prior to the initiation of study treatment unless deemed necessary by the treating physician. (See protocol) * Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment. * Malabsorption syndrome or other condition that precludes enteral route of administration. * Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up. * Unable or unwilling to undergo a screening bone marrow study. * Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.