Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia

Patients must not have had prior treatment with MEC

Patients must not have documented active central nervous system (CNS) involvement by leukemia. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)

Patients must not have received any other investigational or commercial agents or therapies administered with the intention to treat their leukemia within 14 days or 5 elimination half-lives (whichever is shorter) of first receipt of study drug, with the exception of hydroxyurea and/or leukapheresis used to control white blood cell counts

Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9 and CYP2C19 during treatment with M3814. Concomitant use of CYP1A2, CYP2B6 and CYP3A4/5 substrates with a narrow therapeutic index are also excluded during treatment with M3814. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time prior to the first dose of M3814:

* Strong inducers of CYP3A4/5, CYP2C9 and CYP2C19: \>= 3 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814

* Strong inhibitors of CYP3A4/5, CYP2C9 and CYP2C19: \>= 1 week or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814

* Substrates of CYP1A2, CYP2B6 and CYP3A4/5 with a narrow therapeutic index: \>= 1 day prior to the first dose of M3814

Concomitant use of histamine-2 (H2)-blockers or proton pump inhibitors should be avoided as these might affect absorption of M3814; administrations have to be discontinued at least 5 days or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814. Antacid drugs should not be taken 1 hour before and until 2 hours after M3814 administration

Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded

Patients who require oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (including coumadin and warfarin), or who received such agents within 5 days or 5 elimination half-lives (whichever is shorter) of the first dose of M3814. Low and high-molecular weight heparins are permitted provided the platelets are maintained at greater than 30,000/mm\^3

Patients with ongoing active infection or who have received a live attenuated vaccine within 30 days of dosing with M3814

Patients must not have known significant cardiopulmonary disease defined as:

* Unstable angina;

* Congestive heart failure (New York Heart Association \[NYHA\] class III or IV);

* Myocardial infarction (MI) within 6 months prior to first dose. Patients who had ischemic heart disease such as acute coronary syndrome (ACS), MI, and/or revascularization more than 6 months before screening and who are without cardiac symptoms or those with a prior non-ST elevation MI (NSTEM) due to demand-supply mismatch (NSTEM Type II) may enroll

Patients should not have severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect their participation in the study

Patients with psychiatric illness/social situations that would limit compliance with study requirements

Patients should not be pregnant or breastfeeding

A marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., repeated demonstration of a QTc interval \> 480 milliseconds \[ms\] \[CTCAE grade 2\] using Fredericia's QT correction formula)

A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT syndrome)

The use of concomitant medications that prolong the QT/QTc interval

Gastrointestinal disorders that may affect the M3814 absorption

Patients will need to avoid any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days before the first administration of M3814 and throughout the duration of M3814 treatment

What this study is about