| Inclusion Criteria: | 1) Subjects with histologically confirmed myeloid malignancy who have failed standard therapies or are not candidates for palliative therapies. This includes the following:1a) subjects with Acute Myelogenous Leukemia (AML) who are relapsed or refractory to standard therapy; or unsuitable for standard therapy or refuse to receive standard therapy; 1b) subjects with Chronic Myelogenous Leukemia (CML) in accelerated phase that is resistant or refractory to imatinib and dasatinib or nilotinib; 1c) subjects w/ CML in blast crisis that is resistant or refractory to imatinib & dasatinib.
2) CONT # 1: 1d) subjects w/ high-risk Myelodysplastic Syndromes (MDS), defined as Refractory anemia w/ excess blasts (RAEB, 5-19% bone marrow blasts) or Chronic Myelomonocytic Leukemia (CMML) w/ > 5% bone marrow blasts, that is resistant or refractory to standard therapy. 1)e Advanced Myelofibrosis (MF) defined by the presence of at least 1 of the following: POOR PROGNOSTIC features & resistant or refractory to standard therapy; Hemoglobin < 10 gm/dL Platelet count < 100 x 10^9/L WBC count < 4 or > 30 x 10^9/L; Symptomatic splenomegaly, that is >/= 10cm below left costal margin
3) In Phase 2, subjects with CIMF (as well as post-ET/PV MF) requiring therapy, including: 3a) Previously treated CIMF subjects who are now relapsed or previously treated CIMF subjects whose disease was not well-controlled with standard therapy and who have a spleen that is >5 cm below costal margin. 3b) Newly diagnosed subjects with intermediate or high risk CIMF according to the Lille scoring system and who are not suitable for standard therapy,
4) Continuation of Inclusion 3: e.g.: not a candidate for stem cell transplantation; not suitable for hydroxyurea due to cytopenias; are female and unlikely to tolerate androgen therapy; have an excessive need for red blood cell transfusion; no other alternative therapy is available and; have a spleen that is ≥ 5 cm below costal margin.
5) Age >/= 18 years old
6) Eastern Co-operative Oncology Group (ECOG) performance status 0-2
7) Adequate liver and renal function, defined by liver transaminases (AST/SGOT and/or ALT/SGPT) </=2.5 x ULN (AST/ALT </=5 x ULN if liver is involved by malignancy as judged by the investigator) and creatinine </=2.0 mg/dL, or a calculated creatinine clearance of equal to or greater than 60mL/min
8) Has a corrected QT interval (QTc) </= 0.47 seconds using the Bazett Formula
9) At least 2 weeks (from Day 1 of treatment) since prior chemotherapy, biological therapy, radiation therapy, major surgery, or other investigational or anti-cancer therapy that is considered disease-directed and has recovered from prior toxicities to Grade 0-1
10) At least one week (from Day 1 of treatment) since prior treatment with cYP3A4 inducer/inhibitor.
11) All men of reproductive potential and women of child-bearing potential must agree to practice effective contraception during the entire study period and for one month after the last study treatment, unless documentation of infertility exists. Additionally, women of child-bearing potential must have a negative pregnancy test (serum test) within 14 days prior to the first dose of study drug
12) Able to understand and willing to sign the informed consent form |