Phase II Study of the Addition of Azacitidine (IND# 87574, NSC#102816) to Reduced-Intensity Conditioning Allogeneic Transplantation for Myelodysplasia (MDS) and Older Patients With AML
I. To determine if this treatment can improve 2-year progression-free survival (PFS) in
patients with high risk myelodysplastic syndrome (MDS) and in patients with acute myeloid
leukemia (AML) >= 60 yrs age
I. To determine the safety and feasibility of using post-transplantation azacitidine.
II. To determine the ability to use pharmacokinetic-directed busulfan to achieve area under
the curve (AUC) within 20% of target AUC in > 80% of patients.
III. To determine the rate of grade II-IV and III-IV acute graft-vs-host disease (GVHD).
IV. To determine the incidence of extensive chronic GVHD. V. To determine treatment-related
mortality at 100 days and at 1 year. VI. To determine 5-year overall survival.
OUTLINE: This is a multicenter study.
REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV)
over 30 minutes on days -7 to -3, busulfan IV over 45 minutes on days -6 to -3, and
anti-thymocyte globulin IV over 4-10 hours on days -6 to -5 (matched sibling donor [MSD]) or
-6 to -4 (matched unrelated donor [MUD]).
TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day
0 or on days 0-1.
GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV on days -2
to 90 with taper on days 150-180. Patients also receive methotrexate IV on days 1, 3, 6
(MSD), and 11 (MUD).
CONSOLIDATION: Beginning on day 42, patients receive azacitidine subcutaneously (SC) or IV
on days 1-5.
Treatment repeats every 4 weeks for 6 courses. Blood and bone marrow samples may be
collected periodically for correlative and pharmacokinetic studies.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Will be estimated using the Kaplan-Meier product limit estimator.
At 2 years
Cancer and Leukemia Group B
United States: Food and Drug Administration
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|North Shore University Hospital||Manhasset, New York 11030|
|Weill Medical College of Cornell University||New York, New York 10021|
|Mount Sinai Medical Center||New York, New York 10029|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|Beebe Medical Center||Lewes, Delaware 19958|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Dartmouth Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|Florida Hospital||Orlando, Florida 32803|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|
|Cooper Hospital University Medical Center||Camden, New Jersey 08103|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|Monter Cancer Center||Lake Success, New York 11042|
|North Shore-LIJ Health System CCOP||Manhasset, New York 11030|
|Christiana Care Health System-Christiana Hospital||Newark, Delaware 19718|