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
18 Years
N/A
Both
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
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
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
Type of Study:
Interventional
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:
Yes
Principal Investigator
Barry Skikne, M.D., FACP; FCP (SA)
Investigator Role:
Study Director
Investigator Affiliation:
Celgene Corporation
Authority:
United States: Food and Drug Administration
Study ID:
CC-486-AML-002
NCT ID:
NCT01835587
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
Name | Location |
|---|---|
| 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 |
