A Phase 1/2 Dose and Schedule Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Oral Azacitidine (CC-486) in Subjects With Acute Myelogenous Leukemia and Myelodysplastic Syndromes After Allogeneic Hematopoietic Stem Cell Transplantation

Fecha de inicio: 25 de octubre de 2013

Inclusion Criteria: Histologically confirmed Myelodysplastic Syndromes or Acute Myeloid Leukemia undergoing allogeneic hematopoietic stem cell transplantation with either peripheral blood or bone marrow as the source of hematopoietic stem cells At the time of allogeneic HSCT: No prior allogeneic HSCT; and No more than 1 antigen mismatch at Human Leukocyte Antigen (HLA)-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and Bone marrow blast < 20% if MDS or ≤ 10% if AML; and Peripheral blood blast ≤ 5% Be able to start study drug between 42 to 84 days following allogeneic HSCT Post transplant bone marrow blast count ≤ 5% confirmed within 21 days prior to starting study therapy Adequate engraftment within 14 days prior to starting study therapy: Absolute Neutrophil count (ANC) ≥ 1.0 x 10^9/L without daily use of myeloid growth factor; and Platelet count 75 x 10^9/L without platelet transfusion within one week. Adequate organ function: Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN) Serum bilirubin < 2 x ULN Serum creatinine < 2 x ULN Adequate coagulation (Prothrombin time [PT] ≤ 15 seconds, Partial thromboplastin time (PTT) ≤ 40 seconds, and/or International normalized ratio [INR] ≤ 1.5) Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL at screening). Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Must agree to follow protocol-specified pregnancy precautions Exclusion Criteria: Use of any of the following after transplantation and prior to starting oral azacitidine: Chemotherapeutic agents for chemotherapy Investigational agents/therapies Azacitidine, decitabine or other demethylating agents Lenalidomide, thalidomide and pomalidomide Active Graft-versus-host disease (GVHD) grade II or higher Any evidence of gastrointestinal (GI) GVHD Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) Active uncontrolled systemic fungal, bacterial or viral infection Presence of malignancies, other than MDS or AML, within the previous 12 months Significant active cardiac disease within the previous 6 months