Subjects with acute myeloid leukemia or myelodysplastic syndromes in morphological remission after allogeneic hematopoietic stem cell transplantation. MedDRA version: 18.0 Level: LLT Classification code 10000887 Term: Acute myeloid leukemia in remission System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malig
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years at the time of signing the ICD 2. Diagnosis of MDS or AML according to WHO classification undergoing allogeneic HSCT using MAC, NMA or RIC preparative regimens (Bacigalupo, 2009), and with either peripheral blood or bone marrow as the source of hematopoietic stem cells 3. At the time of allogeneic HSCT: • No prior allogeneic HSCT; and • No more than 1 antigen mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and • Bone marrow blast =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Use of any of the following after transplantation and prior to starting study therapy: • Chemotherapeutic agents for chemotherapy (note that prophylactic use of these agents is allowed in this study, eg, methotrexate for GVHD) • Investigational agents/therapies • Azacitidine, decitabine or other demethylating agents • Lenalidomide, thalidomide and pomalidomide 2. Active GVHD grade II or higher 3. Any evidence of gastrointestinal (GI) GVHD 4. Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg 5. Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) 6. Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment) 7. Prior to allogeneic HSCT, history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other GI disorder or defect that may interfere with the absorption, distribution, metabolism or excretion of the Investigational Product and/or predispose the subject to an increased risk of gastrointestinal toxicity 8. Idiopathic thrombocytopenic purpura [ITP], disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura [TTP] 9. Prior history of malignancies, other than MDS or AML, unless the subject has been free of the disease for = 1 year. However, subjects with the following history/concurrent conditions are allowed: • Basal or squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system) 10. Significant active cardiac disease within the previous 6 months, including: • New York Heart Association (NYHA) class III or IV congestive heart failure • Unstable angina or angina requiring surgical or medical intervention; and/or • Myocardial infarction 11. Known or suspected hypersensitivity to azacitidine or mannitol 12. Pregnant or lactating females 13. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 14. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 15. Any condition that confounds the ability to interpret data from the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the maximal tolerated dose (MTD) of oral azacitidine in subjects with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT).;Secondary Objective: 1) To determine the safety and tolerability of oral azacitidine in this subject population. 2) To assess the pharmacokinetics (PK) profile of oral azacitidine and to explore the relationships of azacitidine exposure with safety and efficacy endpoints. 3) To assess the preliminary efficacy of oral azacitidine in this subject population.;Primary end point(s): Maximum tolerated dose (MTD) of oral azacitidine in subjects with AML or MDS after allogeneic HSCT.;Timepoint(s) of evaluation of this end point: At the end of each cycle of Cycles 1 to 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety (type, frequency, severity of AEs and relationship of AEs to oral azacitidine; progression to AML for MDS subjects) - Incidence of acute and chronic graft-versus-host disease (GVHD) - Time to discontinuation from treatment - Plasma PK parameters including, but not limited to, area under the curve (AUC), half-life (t½), observed maximum concentration (Cmax), time at which maximum concentration is observed (tmax), and others as appropriate - Disease recurrence/relapse rate - Time to disease recurrence/relapse - Overall survival and relapse-free survival (RFS) at one year following allogeneic HSCT.;Timepoint(s) of evaluation of this end point: For Safety (which includes Time to discontinuation from treatment) and GVHD: on an ongoing basis; For PK: several time points from Cycle 1 to Cycle 7; For Efficacy (which involves Disease recurrence/relapse rate, Time to disease recurrence/relapse, Overall survival and relapse-free survival (RFS) at one year following allogeneic HSCT): every six months during the first year after transplantation | — |
Countries
United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed