Cladribine Plus Low Dose Cytarabine (LDAC) Alternating With Decitabine in Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

Cohort 1 Inclusion Criteria: 1. Patients with previously untreated AML or high risk MDS (\>/= 10 % blasts or IPSS \>/= intermediate-2). Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML. 2. Age \>/= 60 years. Patients aged \< 60 years who are unsuitable for standard induction therapy may be eligible after discussion with PI 3. Adequate organ function as defined below: * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN) * kidney function (creatinine \< 1.5 x ULN ). 4. ECOG performance status of ≤ 2. 5. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. 6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol. 7. Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine. Exclusion Criteria: 1. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided. 2. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 3. Patient with documented hypersensitivity to any of the components of the chemotherapy program. 4. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Cohort 2 Inclusion Criteria: 8\. Patients with previously untreated AML who are not currently eligible for other frontline clinical trials of AML therapy. Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML. 9\. Age \>/= 18 years who are unsuitable for standard induction therapy are eligible after discussion with PI 10. Patients must have one of the following: * Creatinine \>/= 2 mg/dL * Total bilirubin \>/= 2 mg/dL * ECOG Performance Status equal to 3 or 4 * Is ineligible for participation in a protocol of higher priority 11. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. 12\. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol. 13\. Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine. Exclusion Criteria: 5\. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided. 6\. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, unless these illnesses are judged to be related to the underlying leukemia. 7\. Patient with documented hypersensitivity to any of the components of the chemotherapy program. 8\. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Cohort 3 Inclusion Criteria: 1. Patients with relapsed and or refractory AML who have received at least one prior therapy for their AML. 2. Age \>/= 18 years. 3. Adequate organ function as defined below: * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN) * kidney function (creatinine \< 1.5 x ULN ). 4. ECOG performance status of ≤ 2. 5. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. 6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol. 7. Prior therapy with venetoclax will be allowed. Exclusion Criteria 8. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided. 9. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 10. Patient with documented hypersensitivity to any of the components of the chemotherapy program. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation