Phase II Study of Maintenance Therapy With Decitabine (NSC #127716, IND #50733) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years
I. To determine the efficacy, feasibility, and toxicities when one year of maintenance
therapy with decitabine is given to patients < 60 years with untreated AML who achieve and
maintain first CR following an established induction and intensification regimen.
II. To determine the 1-year disease free survival rate for AML patients in first CR treated
with maintenance decitabine.
I. To measure biologic response to decitabine in evaluable patients with fusion genes to
determine eradication of minimal residual disease.
II. To measure surrogates for DNA demethylation including downregulation of DNMT1 and
induction of fetal hemoglobin.
III. To examine the significance of gene re expression following ex vivo decitabine exposure
in primary AML cells taken at the time of diagnosis on clinical outcome and on gene
expression at the time of relapse after in vivo decitabine exposure.
IV. To continue to evaluate the effectiveness of a cytogenetically risk-adapted approach for
consolidation therapy for patients with CBF or non-CBF AML.
V. To continue the investigation begun in CALGB 19808 aimed at correlation of the rate of
relapse and toxicity with IV busulfan pharmacokinetics when busulfan and etoposide are used
as the preparative regimen for autologous stem cell transplantation for AML patients in
VI. To correlate outcome measures such as CR, DFS, EFS, and OS, with pretreatment
characteristics such as age, sex, race, blood counts, morphology, immunophenotype,
cytogenetics, and molecular features of AML.
OUTLINE: This is a multicenter study.
REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 168 hours on days 1-7 and
daunorubicin hydrochloride IV over 5-10 minutes and etoposide IV over 2 hours on days 1-3.
Patients undergo bone marrow biopsy on day 14. Patients with residual leukemia proceed to
second remission induction therapy. Patients achieving complete remission (CR) proceed to
SECOND REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 120 hours on days
1-5 and daunorubicin hydrochloride IV and etoposide IV over 2 hours on days 1 and 2.
Patients undergo bone marrow biopsy on day 42. Patients with residual leukemia are removed
from the study. Patients achieving CR proceed to intensification therapy.
INTENSIFICATION THERAPY: Patients are stratified and receive intensification therapy
according to cytogenetic findings (favorable cytogenetics [t(8;21)(q22q22),
inv(16)(p13;q22), or t(16;16)(p13;q22) by cytogenetic and/or molecular analysis] vs
unfavorable cytogenetics [all other cytogenetic findings, including normal cytogenetics]).
FAVORABLE CYTOGENETICS: Within 2-4 weeks after achieving CR, patients receive high-dose
cytarabine IV over 3 hours twice daily on days 1, 3, and 5.
Treatment repeats every 28 days for up to 3 courses.
UNFAVORABLE CYTOGENETICS: Peripheral blood stem cell (PBSC) mobilization: Within 2-4 weeks
after achieving CR, patients receive etoposide IV over 96 hours and high-dose cytarabine IV
over 2 hours twice daily on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) once daily
beginning on day 14 and continuing until blood counts recover. Patients then proceed to
PBSC OR BONE MARROW TRANSPLANTATION: Patients receive busulfan IV over 2 hours 4 times daily
on days -7 to -4 and etoposide IV over 4 hours on day -3. Patients undergo autologous PBSC
or bone marrow transplantation on day 0 and receive G-CSF SC once daily beginning on day 0
and continuing until blood counts recover.
UNFAVORABLE CYTOGENETICS AND UNABLE TO UNDERGO PBSC TRANSPLANTATION: Within 2-4 weeks after
achieving CR, patients receive etoposide, high-dose cytarabine, and G-CSF as in unfavorable
cytogenetics (PBSC mobilization) followed by 2 courses of high-dose cytarabine as in
MAINTENANCE THERAPY: Within 60-90 days after completion of intensification therapy, patients
receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 6 weeks for up to 8
Blood and bone marrow samples are obtained periodically during study therapy for cytogenetic
After completion of study treatment, patients are followed up every 2 month for 1 year,
every 6 months for 3 years, and then at 1 year.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of maintenance decitabine administered to patients following intensive induction and consolidation chemotherapy, with or without autologous PSCT
Up to 5 years
Cancer and Leukemia Group B
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Rhode Island Hospital||Providence, Rhode Island 02903|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Western Pennsylvania Hospital||Pittsburgh, Pennsylvania 15224|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|North Shore University Hospital||Manhasset, New York 11030|
|Eastern Maine Medical Center||Bangor, Maine 04401|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Mount Sinai Medical Center||New York, New York 10029|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|
|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|
|Mountainview Medical||Berlin, Vermont 05602|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Miriam Hospital||Providence, Rhode Island 02906|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Blood and Marrow Transplant Group of Georgia||Atlanta, Georgia 30342-1601|
|Dartmouth Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|University Of Vermont||Burlington,, Vermont 05403|
|Florida Hospital||Orlando, Florida 32803|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|
|University of California San Francisco Medical Center-Mount Zion||San Francisco, California 94115|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Nevada Cancer Research Foundation CCOP||Las Vegas, Nevada 89106|
|Cheshire Medical Center-Dartmouth-Hitchcock Keene||Keene, New Hampshire 03431|
|Cooper Hospital University Medical Center||Camden, New Jersey 08103|
|State University of New York Upstate Medical University||Syracuse, New York 13210|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|University of Illinois||Chicago, Illinois 60612|
|Commonwealth Hematology Oncology PC-Worcester||Worcester, Massachusetts 01605|
|University of Missouri - Ellis Fischel||Columbia, Missouri 65203|
|Veterans Administration||Columbia, Missouri 65201|
|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|