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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 Myeloid Leukemia or Myelodysplastic Syndromes After Allogeneic Hematopoietic Stem Cell Transplantation

Phase 1/Phase 2
18 Years
Not Enrolling
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

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Trial Information

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 Myeloid Leukemia or Myelodysplastic Syndromes After Allogeneic Hematopoietic Stem Cell Transplantation

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.

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:

- Absoulute Neutrophil count (ANC) ≥ 1.0 x 109/L without daily use of myeloid growth
factor; and

- Platelet ≥ 25 x 109/L without platelet transfusion within 1 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)

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

To determine the maximal tolerated dose of oral Azacitidine in participants with AML or MDS after allogeneic HSCT

Outcome Time Frame:

30 months

Safety Issue:


Principal Investigator

Barry Skikne, M.D., FACP; FCP (SA)

Investigator Role:

Study Director

Investigator Affiliation:

Celgene Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

June 2013

Completion Date:

September 2016

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Acute myeloid leukemia,
  • myelodysplastic syndromes,
  • CC-486, oral Azacitidine,
  • transplantation,
  • allogeneic,
  • HSCT.
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



MD Anderson Cancer CenterHouston, Texas  77030-4096
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University Hospitals Case Medical CenterCleveland, Ohio  44106