PF-04449913 For Patients With Acute Myeloid Leukemia at High Risk of Relapse After Donor Stem Cell Transplant

Inclusion Criteria:

WHO-confirmed AML
Age ≥18 years
Between days 28 and 50 post transplantation at the time of initiation of the study drug
ECOG performance status ≤ 2 (See Appendix A: ECOG Performance Status Scale)
Life expectancy > 2 months

Recipient of a myeloablative or non-myeloablative allogeneic HSCT

Conditioning regimen to be prescribed at investigator's discretion, but will be prospectively defined as myeloablative or non-myeloablative
Stable engraftment, as defined by absolute neutrophil count (ANC) ≥ 1000/mm3 and platelets ≥ 25,000/mm3
In morphologic remission (< 5% marrow blasts) based on BM biopsy performed +/- 5 days of day 28 post- transplantation
Without clinical signs of active central nervous system disease
For non-myeloablative transplants, ≥50% CD3 donor chimerism at screening
High risk of relapse after HSCT, defined as the presence of minimal residual disease as measured by flow cytometry in the absence of evidence of morphologic disease on a bone marrow biopsy prior to HSCT

Adequate organ function as indicated by the following laboratory values:

Aspartate aminotransferase (AST), alanine aminotransferase, (ALT) ≤ 3.0 x institutional upper limit of normal (ULN)
Total bilirubin ≤ 2.0 x institutional ULN, unless documented Gilbert's syndrome
Either creatinine <1.5 x institutional upper limit of normal (ULN) or creatinine clearance >60 mL/min as calculated by institution's standard formula
Serum/urine pregnancy test (for females of childbearing potential) that is negative within 72 hours prior to initiation of first dose of treatment (a patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active)
Female patients of childbearing potential and sexually active males and female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of assigned treatment.
Subject is able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
Use of any other experimental drug or therapy within 28 days of baseline
Inability to swallow or absorb drug
Active uncontrolled acute fungal, bacterial, or other infection that is unresponsive to therapy at time of study drug dosing
Unstable angina pectoris
New York Heart Association Class III or IV heart failure
QTc interval (using Fridericia's correction formula, QTcF, if prolonged) >470 msec
Active cardiac arrhythmias with rapid ventricular response (defined as heart rate greater than 100 beats/minute)
Known HIV infection
Grade III/IV acute GVHD
Current use or anticipated need for food or drugs that are known moderate/strong CYP3A4 inducers (See Table 1 and section 5.9.2: Prohibited Concomitant Therapy), with the exception of azole antifungals, which are permitted.
Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.
Pregnant or lactating females