Clinical Research Directory

Inclusion Criteria: * Age ≥ 18 years * Diagnosis of high grade myeloid neoplasm (\> 10% blasts in blood or marrow), other than acute promyelocytic leukemia (APL) according to the 2022 International Consensus Classification (ICC) classification. Patients with acute leukemias of ambiguous lineage are eligible * The use of cytoreductive therapy before treatment is permitted. Patients with symptoms/signs of leukostasis, white blood cell (WBC) \> 100,000/μL, or acute symptoms that in the opinion of the treating physician are likely related to their high-grade myeloid neoplasm may receive up to 2 doses of cytarabine (up to 500 mg/m\^2 each) prior to study day 1 * Patients may have received treatment for antecedent low-grade myeloid neoplasm (\< 10% myeloid blasts on blood or bone marrow) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3 (for patients aged \< 75 years) or ECOG performance status of 0 - 2 (for patients aged ≥ 75 years) * The presence of one or more of the following criteria for 'unfitness'. (Patients without respiratory symptoms at rest are eligible and should only complete spirometry/diffusion capacity of the lung for carbon monoxide \[DLCO\] measurements as clinically indicated): * ECOG Performance Status of 2 or 3 * Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina * Documented DLCO ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; or dyspnea at rest, or requiring supplemental oxygen * Creatinine clearance ≥ 30 mL/min to \< 45 ml/min * Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN) * Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy * Adequate cardiac function: * Patients aged ≤ 60 years without a history of cardiac disease or evidence of heart failure are eligible if they also exhibit the following: * Chest x-ray (CXR) without evidence of moderate or severe pulmonary edema or pleural effusion, and a normal cardio-mediastinal silhouette * Electrocardiogram (ECG) without evidence of atrial or ventricular chamber enlargement * Note that patients with either abnormal CXR or ECG should have a structural heart assessment (echocardiogram, multigated acquisition scan \[MUGA\] or similar) and are eligible if left ventricular ejection fraction (LVEF) \> 40% and the abnormalities in the CXR/ECG do not preclude safe administration of intensive chemotherapy * Patients with a documented left ventricular ejection fraction (LVEF) ≥ 40%, assessed within 3 months prior to registration, e.g. by MUGA scan or echocardiography, or another appropriate diagnostic modality are eligible * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x ULN, unless judged due to leukemic organ involvement * Total bilirubin ≤ 3 x ULN unless judged due to leukemic organ involvement, Gilbert's syndrome, or hemolysis * Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Known hypersensitivity to cytarabine, anthracycline, hypomethylating agents, or venetoclax * Cardiovascular disability status of New York Heart Association class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain * Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal) * Concomitant illness associated with a likely survival of \< 1 year * Active pregnancy or breast feeding