Study of MK-8242 Alone and in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia (P07649)
Study of MK-8242 Alone and in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia (P07649)
This is a study of MK-8242 alone and in combination with cytarabine in adult participants
 with refractory or recurrent acute myelogenous leukemia (AML). The study will have 2 Arms.
 Arm A is for participants with refractory or recurrent AML who are considered ineligible for
 standard chemotherapy. In Part 1 of Arm A, participants will receive MK-8242 monotherapy in
 escalating doses to determine the recommended phase 2 dose [RP2D]. In Part 2, participants
 will receive monotherapy with MK-8242 to confirm the RP2D and assess preliminary efficacy.
 Arm B is for participants with recurrent AML following an initial complete remission (CR) or
 CR with incomplete marrow recovery (CRi) of 6 to 12 months duration. In Part 1 of Arm B,
 participants will receive MK-8242 in escalating doses + cytarabine to determine the RP2D in
 combination with cytarabine. In Part 2, participants will receive MK-8242 + cytarabine to
 confirm the RP2D and assess preliminary efficacy. The pharmacokinetics of MK-8242 will be
 studied in both arms. With Amendment 4 (22 August 2013) a 21-day dosing cycle is added, with
 MK-8242 being given on Days 1-7 of each 21-day cycle in both the monotherapy and combination
 therapy arms; data from Arm A will be used to determine whether a participant receives 21-day
 or 28-day therapy in Arm B.
Inclusion criteria:

 -  For Arm A Part 1 (monotherapy/dose escalation): refractory or recurrent AML, not an
 appropriate candidate for standard therapy

 -  For Arm A Part 2 (monotherapy/dose confirmation/cohort expansion): refractory or
 recurrent AML, not an appropriate candidate for standard therapy, and have wild type
 p53 gene mutation analysis

 -  For Arm B Part 1 (combination therapy/dose escalation): recurrent AML having achieved
 an initial CR or CRi of 6-12 months duration and age ≥18 years old and <70 years old

 -  For Arm B Part 2 (combination therapy/dose confirmation/cohort expansion): recurrent
 AML having achieved an initial CR or CRi of 6-12 months duration, age ≥18 years old
 and <70 years old, and have wild type P53 gene mutation analysis

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for all Arm
 A, or 0 or 1 for all Arm B

 -  Negative pregnancy test within 72 hours of the first dose of study medication

 -  Female participants and male participants and their partners who are of childbearing
 potential must agree to abstain from sexual intercourse or to use an acceptable method
 of contraception during the study and for 90 days following the last dose of study
 therapy

 -  Adequate organ function

 -  Recovered from the effects of any prior surgery, radiotherapy or anti-neoplastic
 treatment, with the exception of alopecia

 -  Must be able to swallow, retain, and absorb oral medications and oral nutrition

 -  Must follow the appropriate washout period for prohibited treatments

 Exclusion criteria:

 -  Active malignancy other than AML

 -  Leptomeningeal leukemia requiring intrathecal therapy

 -  For Arm A and B, Part 1 only: history of myelodysplastic syndrome (MDS)

 -  For Arm A and B, Part 2: AML in the background of MDS may be included

 -  Isolated extramedullary leukemia without also meeting bone marrow criteria for acute
 leukemia

 -  AML blast crisis of chronic myelogenous leukemia (CML)

 -  Bone marrow transplant with active graft-versus host disease (GVHD) or who receives
 immunosuppressive therapy

 -  Uncontrolled active infection that requires systemic treatment

 -  Clinically significant hepatitis at Screening, or hepatitis C antibody positive,
 hepatitis B surface antigen positive, or human immunodeficiency virus (HIV)
 seropositive

 -  Persistent, unresolved, drug-related toxicity

 -  Breast-feeding, pregnant, intends to become pregnant or intends to breast feed during
 the study or has a positive pregnancy test at Screening

 -  A person participating in any other clinical study with a potentially therapeutic
 agent or who has received another investigational product within 5 half-lives (if the
 half-life is known) or 28 days (if the half-life is unknown) prior to Day 1 of cycle 1

 -  A participant who, within the past 6 months, has had any of the following: myocardial
 infarction, coronary/peripheral artery bypass graft, cerebrovascular accident,
 transient ischemic attack, or uncontrolled seizure disorder (i.e., seizures within the
 past 6 months)

 -  A participant who, at the time of Screening, presents with: unstable or uncontrolled
 angina, New York Heart Association (NYHA) class III or IV congestive heart failure,
 uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically
 significant electrocardiogram (ECG) abnormality

 -  Known bleeding disorder, e.g. hemophilia or disseminated intravascular coagulopathy or
 on anti-coagulation therapy

 -  For Arm B only: Known hypersensitivity to cytarabine