This trial is active, not recruiting.

Conditions leukemia, myeloid, acute, myelodysplastic syndromes
Treatment oral azacitidine
Phase phase 1/phase 2
Sponsor Celgene Corporation
Start date July 2013
End date October 2016
Trial size 31 participants
Trial identifier NCT01835587, CC-486-AML-002


The purpose of the study is to determine the maximal tolerated dose and schedule of CC-486 (also known as oral Azacitidine) in patients with AML or MDS after allogeneic HSCT. Allogeneic hematopoietic stem cell transplantation (HSCT) is more frequently used in Acute Myloid leukemia (AML) or Myelodysplastic Syndromes (MDS) as a potential curative therapy. However, disease recurrence/relapse and graft-versus-host disease (GVHD) remain the principal causes of fatal complications after transplantation. Azacitidine has significant activity in MDS and AML. Azacitidine has also demonstrated immunomodulatory activity in AML patients after allogeneic HSCT. An oral formulation of Azacitidine provides a convenient route of administration and an opportunity to deliver the drug over a prolonged schedule.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Dose of 150mg, 200mg, or 300mg once daily (QD) for the first 7, 10, or 14 days of each 28-day cycle, starting 42-84 days after transplantation.
oral azacitidine
Cohorts of 3 to 6 subjects will be treated at escalating or de-escalating sequential dose levels until a preliminary MTD is identified.

Primary Outcomes

Maximum tolerated dose
time frame: 30 months

Secondary Outcomes

Adverse Events
time frame: 30 months
Acute and Chronic GVHD
time frame: 30 months
Time to discontinuation from treatment
time frame: 30 months
Pharmacokinetics - Cmax
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - Tmax
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - AUC (0-t)
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - AUC (0-∞)
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - λz
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - t ½
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - CL/F
time frame: Day 1 of cycles 1 and 2
Pharmacokinetics - Vd/F
time frame: Day 1 of cycles 1 and 2
Relapse Rate
time frame: 30 months
Relapse Time
time frame: 30 months
Overall survival at one year
time frame: 12 months
Relapse-free survival (RFS) at one year
time frame: 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed (Myelodysplastic Syndromes) MDS or Acute Myeloid Leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) 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 therapy 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 109/L without daily use of myeloid growth factor; and - Platelet count 75 x 109/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

Additional Information

Official title 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
Description This is an open-label, multicenter study of oral Azacitidine in MDS or AML patients who have undergone allogeneic HSCT. The study consists of three phases: Screening, Treatment and Follow-up. During the Screening phase, which will take place within 4 weeks before starting oral Azacitidine, the study doctor will do tests to see if the patient is suitable for this study. The patient meeting protocol-specified entry criteria will enter the Treatment phase and be assigned to receive oral Azacitidine at 200 or 300 mg once daily (QD) for the first 7 or 14 days of each 28-day cycle. The dosing group of 200 mg QD on Days 1 to 7 will be evaluated first (ie, Cohort 1). In the event that unacceptable toxicity occurs in Cohort 1, then oral Azacitidine may be evaluated at lower dose levels (eg, 150 mg). If the dosing regimen is confirmed to be safe in Cohort 1, other cohorts will be evaluated sequentially. During the treatment phase, subjects will be monitored closely for safety and tolerability. Dosing interruption or delay, dose or schedule reduction, intra-subject dose/schedule escalation or re-escalation may occur on the basis of protocol-specified dosing adjustment guidelines. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by vital signs, physical examination, performance status, laboratory tests and evaluation of adverse events. The patient can continue to receive the study treatment for up to 12 months provided that they benefit from the study treatment and all protocol-specified criteria are met. However, the patient may receive the study treatment for less than 12 months due to adverse event, disease recurrence or progression. When the study treatment is discontinued, all patients who have received at least one dose of oral Azacitidine will be asked to see the study doctor for the Treatment Discontinuation visit. Thereafter, all patients discontinued from the study treatment will enter the Follow-up phase for safety and survival follow up.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Celgene Corporation.