WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

Exclusion Criteria

• •Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, known positive for active infectious hepatitis, type A, B or C (past infection allowed), or psychiatric illness/social situations that would limit compliance with study requirements; Note: ongoing infection controlled on antibiotics/antifungal/antiviral medications are allowed
• •Any of the following prior therapies:
• •* Cytotoxic chemotherapy =\<14 days prior to registration
• •* Immunotherapy =\< 14 days prior to registration
• •* Biologic therapy (i.e. antibody therapies) =\< 14 days prior to registration
• •* Radiation therapy =\<14 days prior to registration
• •* Targeted therapies (i.e. kinase inhibitors, =\< 7 days or 5 half-life's whichever is shorter)
• •• For steroids or other non-cytotoxics given for blast count control, patient must be off for \> 24 hours (hrs) before starting therapy; NOTE: hydroxyurea (HU) is allowed for blast count control throughout study
• •* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =\< 14 days prior to registration
• •Active uncontrolled central nervous system (CNS) leukemia; NOTE: positive (cyto)pathology is allowed and patient can receive intrathecal chemotherapy
• •Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• •Any previous treatment with AZD1775 or allergic reactions to excipients of AZD1775
• •Acute promyelocytic leukemia (APL, M3) unless failed regimens that included tretinoin, arsenic trioxide, anthracyclines and cytarabine and currently NOT candidates for stem cell transplantation
• •Major surgery =\< 28 days prior to registration
• •Clinically significant heart disease, including the following:
• •* Active severe angina pectoris within 3 months prior to registration
• •* Acute myocardial infarction within 3 months prior to registration
• •* New York Heart Association classification IV cardiovascular disease or symptomatic class III disease
• •* Note: patients with any of the above may be allowed after discussion amongst the investigators including the principal investigator
• •Any of the following:
• •* Pregnant women
• •* Nursing women
• •* Men or women of childbearing potential who are unwilling to employ adequate contraception
• •Subject has had prescription or non-prescription drugs or other products known to be sensitive cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior (alternatively 5 half lives if T1/2 is known) prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug
• •* NOTE: co-administration of aprepitant or fosaprepitant during this study is prohibited
• •* Note: individual drugs exerting CYP interactions may be continued on a case by case basis if felt essential for patient management, after discussions and discretion of the treating physician
• •* The preferred azole anti-fungal medication is fluconazole (alternatively posaconazole) which can be given during treatment with AZD1775 at the treating physician's discretion, however with dose reductions of AZD1775 by 25-75% (i.e. from AZD1775 200mg to 150 or 100mg)
• •Patients may not be on an inhibitor of breast cancer resistance protein (BCRP)
• •* NOTE: AZD1775 is an inhibitor of breast cancer resistance protein (BCRP); the use of statins including atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives
• •Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study; NOTE: orange juice is allowed
• •Corrected QT interval (QTc) \> 470 msec (as calculated per institutional standards) at study entry or congenital long QT syndrome