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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
To determine the maximal tolerated dose of oral Azacitidine in participants with AML or MDS after allogeneic HSCT
Barry Skikne, M.D., FACP; FCP (SA)
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University Hospitals Case Medical Center||Cleveland, Ohio 44106|