Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia With Myelodysplasia-Related ChangesAdult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2AUntreated Adult Acute Myeloid LeukemiaAdult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11Acute Myeloid Leukemia
- Interventions
- Procedure: Autologous Bone Marrow TransplantationProcedure: Autologous Hematopoietic Stem Cell TransplantationBiological: FilgrastimOther: Laboratory Biomarker AnalysisOther: Pharmacological Study
- Registration Number
- NCT00416598
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial is studying the side effects and how well decitabine works when given as maintenance therapy after standard therapy in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin, etoposide, busulfan, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine as maintenance therapy after standard therapy may keep cancer cells from coming back.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the efficacy, feasibility, and toxicities when one year of maintenance therapy with decitabine is given to patients \< 60 years with untreated acute myeloid leukemia (AML) who achieve and maintain first complete remission (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.
SECONDARY OBJECTIVES:
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 deoxyribonucleic acid (DNA) demethylation including downregulation of DNA methyltransferase 1 (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 core binding factor (CBF) or non-CBF AML.
V. To continue the investigation begun in Cancer and Leukemia Group B (CALGB) 19808 aimed at correlation of the rate of relapse and toxicity with intravenous (IV) busulfan pharmacokinetics when busulfan and etoposide are used as the preparative regimen for autologous stem cell transplantation for AML patients in first CR.
VI. To correlate outcome measures such as complete response (CR), disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), with pretreatment characteristics such as age, sex, race, blood counts, morphology, immunophenotype, cytogenetics, and molecular features of AML.
OUTLINE:
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 intensification therapy.
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 transplantation.
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 favorable genetics.
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 courses.
After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 546
-
Unequivocal histologic diagnosis of AML (> 20% blasts in the bone marrow based on the World Health Organization [WHO] and/or French American British [FAB] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there were no bone marrow biopsy showing myelodysplastic syndrome (MDS) > 3 months prior to enrollment; patients with therapy-related AML are eligible if they have been free of their primary disease and have not received any chemotherapy for at least 2 years
-
No prior 5-azacitidine or decitabine therapy
-
No prior treatment for leukemia or myelodysplastic syndrome with four permissible exceptions:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea
- Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
- Growth factor/cytokine support
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy, PBSC or bone marrow transplantation) Pharmacological Study See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Daunorubicin Hydrochloride See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Etoposide See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Autologous Hematopoietic Stem Cell Transplantation See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Autologous Bone Marrow Transplantation See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Laboratory Biomarker Analysis See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Filgrastim See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Busulfan See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Cytarabine See Detailed Description. Treatment (chemotherapy, PBSC or bone marrow transplantation) Decitabine See Detailed Description.
- Primary Outcome Measures
Name Time Method Number of Participants Who Completed Maintenance Decitabine. Up to 5 years To determine feasibility of decitabine maintenance, this outcome measures the number of participants who completed all 8 planned cycles of decitabine maintenance as per protocol.
Disease-free Survival (DFS) Rate at 1 Year At 1 year For participants who achieved a complete remission (CR), this is the percentage of participants who were alive and relapse free at 1 year. The 1 year rate, with 95% confidence interval, was estimated using the Kaplan-Meier method
A CR is defined as those with \> 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, \<5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils \> 1000 mL and platelets \>= 100,000 mL).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (46)
Northwell Health NCORP
🇺🇸Lake Success, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
🇺🇸Fort Wayne, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Commonwealth Hematology Oncology PC-Worcester
🇺🇸Worcester, Massachusetts, United States
Veterans Administration
🇺🇸Columbia, Missouri, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Great Plains Health Callahan Cancer Center
🇺🇸North Platte, Nebraska, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Cheshire Medical Center-Dartmouth-Hitchcock Keene
🇺🇸Keene, New Hampshire, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Vermont College of Medicine
🇺🇸Burlington, Vermont, United States
Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸Berlin, Vermont, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States