Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

Clinical picture indicative of leukostasis or evidence of disseminated intravascular coagulopathy

Other investigational agent within 3 weeks prior to initiation of study therapy

Ongoing toxicities \>= grade 2 from prior therapy

Acute promyelocytic leukemia (APL, M3)

Active central nervous system (CNS) leukemia

History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD1775 or belinostat

Stem cell transplant within previous 3 months prior to initiation of study therapy

Major surgical procedures =\< 28 days before beginning study treatment or minor surgical procedures =\< 7 day before beginning study treatment; no waiting required after placement of a vascular access device

Uncontrolled infection

Pregnant or nursing; women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study therapy

* Note: Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AZD1775/belinostat

Circulating blast count \>= 50,000/uL within the week preceding enrollment

Current candidacy for a potentially curative allogeneic stem cell transplant, unless declined

Corrected QT (QTc) interval \>= 450 ms (ie, grade 1 or higher) on electrocardiogram (ECG) prior to initiation of study treatment

* If baseline QTc on screening ECG is \>= 450 ms (ie, grade 1 or higher):

* Check potassium and magnesium serum levels

* Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval

* For patients with baseline heart rate (HR) \< 60 beats per minute (bpm) or \> 100 bpm, manual measurement of QT interval by cardiologist is required, with Fridericia correction applied to that manual measurement to determine the QTc for eligibility consideration

* Note: For patients with HR 60-100 bpm, manual measurement of QTc interval and use of Fridericia calculation is NOT required

Any of the following related to risk of torsades de pointes and sudden cardiac death:

* History of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator

* Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia; agents used for rate-control of atrial fibrillation are permitted provided that they are not prohibited due to potential drug interactions

* Known congenital long QT syndrome

* Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate \< 50 bpm or \> 120 bpm

Unstable angina, myocardial infarction or New York Heart Association (NYHA) class III/IV congestive heart failure within 30 days preceding study enrollment

Ongoing or planned treatment with any of the following:

* Atorvastatin

* Strong inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product

* If any of these agents have been used, patients must be off them for \>= 2 weeks before starting study treatment

Any known UGT1A polymorphism, heterozygous or homozygous

History of prior therapy with belinostat or AZD1775

Active gastrointestinal (GI) conditions that might predispose to drug intolerance or poor drug absorption

Receiving any other therapies for cancer treatment (with the exception of gonadotropin-releasing hormone \[GnRH\] agonists for prostate cancer); Note: hydroxyurea is allowed before initiation of study treatment and for the first 5 days of study treatment

Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy

Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk, interfere with the patient's participation in the study, or hinder evaluation of study results

What this study is about