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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02085408
Other study ID # E2906
Secondary ID NCI-2011-01992CD
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date February 4, 2011
Est. completion date October 2024

Study information

Verified date June 2023
Source Eastern Cooperative Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This randomized phase III trial studies clofarabine to see how well it works compared with daunorubicin hydrochloride and cytarabine when followed by decitabine or observation in treating older patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as clofarabine, daunorubicin hydrochloride, cytarabine, 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 more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective in treating acute myeloid leukemia.


Description:

PRIMARY OBJECTIVES: I. To evaluate the effect of clofarabine induction and consolidation therapy on overall survival in comparison with standard therapy (daunorubicin [daunorubicin hydrochloride] & cytarabine) in newly-diagnosed acute myeloid leukemia (AML) patients age >= 60 years. SECONDARY OBJECTIVES: I. To evaluate complete remission (CR) rates, duration of remission, and toxicity/treatment-related mortality of clofarabine in comparison with standard therapy (daunorubicin & cytarabine) in newly-diagnosed AML patients age >= 60 years. II. To evaluate the feasibility of consolidation with reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical donors in patients who achieve a response to induction therapy, including the incidence of successful engraftment, acute and chronic graft-versus-host disease, transplant-related mortality, and its impact on overall survival in comparison to patients receiving chemotherapy. III. To evaluate the duration of remission and disease-free survival of patients in complete remission following completion of consolidation therapy who are subsequently randomized to receive scheduled low-dose decitabine maintenance in comparison with observation. IV. To perform expression and methylation profiling on all patients receiving decitabine and to correlate their integrated epigenetic signatures with response to decitabine. V. To examine the epigenetic profiles of remission marrow in patients randomized to observation vs. decitabine to determine whether epigenetic signature of apparently morphologically normal bone marrow is predictive of relapse or response to decitabine maintenance. VI. To explore the possible association of response to clofarabine with ABC-transporter P-glycoprotein (Pgp). VII. To assess the intensity of expression of CXC chemokine receptor type 4 (CXCR4) on diagnostic leukemia cells and to correlate this parameter with other established prognostic factors. VIII. To assess the entire spectrum of somatic mutations and affected pathways at diagnosis of AML and elucidate the association between gene mutation and outcome. IX. To examine the impact of smoking, obesity, regular acetaminophen use, regular aspirin use, benzene exposure, living in a rural/farm environment and some other underlying exposures and lifestyle factors associated with AML development on overall survival (OS). X. To investigate potential correlative results between array comparative genomic hybridization (CGH) findings and acute myeloid leukemia patient characteristics. TERTIARY OBJECTIVES: I. To compare health-related quality of life (QOL) (physical, functional, leukemia-specific well-being) and fatigue in elderly AML patients receiving standard induction therapy with those receiving clofarabine. II. To measure the change in health-related QOL that occurs over time (within treatment groups). III. To comprehensively assess patient function at the time of study enrollment. IV. To determine if components of a comprehensive geriatric assessment or QOL scales predict ability to complete AML treatment. V. To describe the impact of transplant on QOL in AML patients above age 60. OUTLINE: INDUCTION THERAPY: Patients are randomized to 1 of 2 treatment arms. ARM A (STANDARD THERAPY): Patients receive daunorubicin hydrochloride at 60 mg/m^2 intravenously (IV) over 10-15 minutes on days 1-3 and cytarabine at 100 mg/m^2 IV continuously on days 1-7. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., < 5% blasts and < 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 14. ARM B: Patients receive clofarabine at 30 mg/m^2 IV over 1 hour on days 1-5. Patients with residual disease or those who do not achieve an aplastic bone marrow on day 12-14 (i.e., < 5% blasts and < 20% cellularity or markedly/moderately hypocellular) may receive a second course of induction therapy beginning no sooner than day 21 and no later than day 56. Patients who achieve a complete remission (CR) or CR with incomplete marrow recovery (CRi) after induction therapy proceed to consolidation therapy (Arms C and D). Patients who are 60-69 years of age who achieve a "morphologic leukemia-free state" after induction therapy and who have an HLA-identical donor proceed to allogeneic stem cell transplantation. CONSOLIDATION THERAPY: Beginning within 60 days after documentation of CR or CRi, patients receive consolidation therapy in the same arm they were randomized to for induction therapy. ARM C (STANDARD THERAPY): Patients receive cytarabine at 1500 mg/m^2 IV over 1 hour once or twice daily on days 1-6. Treatment repeats every 4-6 weeks for 2 courses. ARM D: Patients receive clofarabine at 20 mg/m^2 IV over 1 hour on days 1-5. Treatment repeats every 4-6 weeks for 2 courses. Patients who remain in CR after completion of consolidation therapy are randomized to one of the two maintenance therapy arms (Arms E and F). MAINTENANCE THERAPY: Beginning within 60 days after completion of consolidation therapy, patients receive maintenance therapy and are randomized to 1 of 2 arms. Patients not eligible for randomization to decitabine maintenance after recovery from consolidation will be followed according to Arm E. ARM E: Patients undergo observation monthly for 12 months. ARM F: Patients receive decitabine at 20 mg/m^2 IV over 1 hour on days 1-3. Treatment repeats every 4 weeks for 12 months the absence of unacceptable toxicity. ALLOGENEIC STEM CELL TRANSPLANTATION WITH REDUCED-INTENSITY CONDITIONING REGIMEN (Arm G): Patients begin reduced-intensity conditioning 30-90 days after the initiation of induction therapy. CONDITIONING REGIMEN: Patients receive fludarabine phosphate at 30 mg/m^2 IV over 30 minutes on days -7 to -3, busulfan at 0.8 mg/kg IV over 2 hours every 6 hours on days -4 and -3 (for a total of 8 doses), and anti-thymocyte globulin at 2.5 mg/kg/day IV over 4-6 hours on days -4 to -2. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. After completion of study treatment, patients are followed up every 3 months for 4 years, every 6 months for 1 year, and then annually thereafter.


Other known NCT identifiers
  • NCT01041703

Recruitment information / eligibility

Status Active, not recruiting
Enrollment 727
Est. completion date October 2024
Est. primary completion date February 22, 2021
Accepts healthy volunteers No
Gender All
Age group 60 Years and older
Eligibility Inclusion Criteria for Step 1 (Induction): - Sexually active males must be strongly advised to use an accepted and effective method of contraception - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin =< grade 1 - Newly-diagnosed AML patients according to World Health Organization (WHO) classification who are considered candidates for intensive chemotherapy based upon examination of peripheral blood or bone marrow aspirate specimens or touch preparations of the bone marrow biopsy obtained within two weeks prior to randomization; a bone marrow aspirate is required for enrollment; however, on occasion there is discordance between percentage of myeloblasts on the differential of the peripheral blood or aspirate; the peripheral blood criteria are sufficient for diagnosis; confirmatory immunophenotyping will be performed centrally - ECOG performance status (PS) 0-3 (restricted to ECOG PS 0-2 if >= 70 years of age) - Patients with secondary AML are eligible for enrollment onto the trial; secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML - Total serum bilirubin =< 1.5 times upper limit of normal (ULN) (=< grade 1); if total bilirubin is 2 to 3 mg/dL, but direct bilirubin is normal, then the patient will be considered eligible - Patients with a serum creatinine > 1 are eligible if they have a calculated glomerular filtration rate (GFR) of >= 60 ml/min (i.e. class I or class II chronic kidney disease ) using the Modification of Diet in Renal Disease (MDRD) formula - Note: Daily creatinine and MDRD formula are only for the 1st induction cycle - Cardiac ejection fraction >= 45% or within institutional normal limits; a nuclear medicine gated blood pool examination is preferred; a two-dimensional (2-D) echocardiogram (ECHO) scan is acceptable if a calculated ejection fraction is obtained and follow-up measurement of the cardiac ejection fraction will also be performed by echocardiography; measurement of cardiac ejection fraction should be within two weeks prior to receiving treatment - NOTE: when a multi gated acquisition scan (MUGA) or echocardiogram cannot be obtained due to weekend or holiday, then patients may be enrolled provided there is no history of significant cardiovascular disease and a measurement of cardiac ejection fraction will be performed within 5 days of study enrollment - Patients with suspected central nervous system (CNS) involvement should undergo lumbar puncture - Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (>10^9/l) from peripheral blood - HLA typing should be performed at registration, if possible - Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing Exclusion Criteria for Step 1 (Induction): - Concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS]) - Active, uncontrolled infection - Acute promyelocytic leukemia (APL) confirmed either by the presence of t(15;17)(q22;q21) or promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha transcripts - Blastic transformation of chronic myelogenous leukemia - Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine - Prior chemotherapy for AML with the exception of hydroxyurea for increased blast count or leukapheresis for leukocytosis - Documented CNS involvement - Previous treatment for antecedent hematological disorders (AHD) with 5-azacitidine, decitabine, or low dose cytarabine - Human immunodeficiency virus (HIV) infection Inclusion Criteria for Step 2 (Consolidation) - NOTE: All patients achieving complete remission (CR) or complete remission with incomplete blood count recovery (CRi) will receive consolidation when fit - NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation treatment - Consolidation cycle 1 must commence within sixty days of the bone marrow aspirate and biopsy that confirmed the presence of a CR or CRi - Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant) - Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi - ECOG performance status of 0-2 - Patients must have resolved any serious infectious complications related to induction - NOTE: Patients with an HLA-matched donor and proceeding to transplant will be allowed up to one cycle of consolidation treatment - Any significant medical complications related to induction must have resolved - Patients must have a creatinine and AST =< grade 1 within 48 hours prior to registration Inclusion Criteria for Step 3 (Maintenance): - Maintenance should commence within 60 days of recovery of peripheral blood counts after consolidation cycle 2; patients must begin consolidation cycle 2 within 60 days of recovery to be eligible for further therapy - Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy and cytogenetic analysis - ECOG performance status of 0 -2 - Patients must have resolved any serious infectious complications related to consolidation cycle 2 - Any significant medical complications related to consolidation cycle 2 must have resolved - Total serum bilirubin =< 1.5 x ULN - NOTE: if total bilirubin is 2-3 mg/dL, but direct bilirubin is normal, then the patient will be considered eligible - Serum creatinine =< grade 1 - The absolute neutrophil count (ANC) must be > 1000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover - The platelet count must be > 75,000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover Inclusion Criteria for Step 3 (Allogeneic Transplantation): - Patients must be > 28 days from the start of induction or re-induction chemotherapy, or from the start Consolidation Cycle 1 (if received) and < 90 days following recovery from most recent treatment; and they must have achieved and maintained a response to induction therapy (CR, CRi, or "morphologic disease-free state") - Patients must have recovered from the effects of induction, re-induction, or consolidation chemotherapy (all toxicities =< grade I with the exception of reversible electrolyte abnormalities), and have no ongoing active infection requiring treatment - Patients must have a total serum bilirubin =< 1.5 x ULN (grade =< 1) and a serum creatinine =< grade 1; AST <= grade 1 - An eligible HLA-identical donor (either related or unrelated) should be available; in sibling donors, low resolution HLA typing (A,B,DR) will be considered sufficient; in the case of unrelated donors, high-resolution class I and II typing (A, B, C, DRB1 and DQ) should be matched at all 10 loci; donors must be willing and able to undergo peripheral blood progenitor mobilization - HLA-identical sibling (6/6): the donor must be determined to be an HLA-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1) - Matched unrelated donor (10/10): high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRBL, and -DQB1 - NOTE: for matched donors - will allow select 1 antigen mismatched sibling donors and unrelated donors in accordance with site institutional standard, as long as matched at HLA-A, HLA-B, HLA-C, and DRB1, and with advanced discussion/approval by the Study Chair and the bone marrow transplant (BMT) co-chair - Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance - Patients must have a cardiac ejection fraction of >= 40%, or within institutional normal limits; a nuclear medicine gated blood pool examination is preferred; a 2-D ECHO scan is acceptable if a calculated ejection fraction is obtained and follow-up measurement of the cardiac ejection fraction will also be performed by echocardiography; measurement of cardiac ejection fraction should be within two weeks prior to allogeneic transplantation - Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease Exclusion Criteria for Step 3 (Allogeneic Transplantation): - Hypersensitivity to Escherichia (E.) coli-derived products - Human immunodeficiency virus (HIV) infection; patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies

Study Design


Related Conditions & MeSH terms

  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myelomonocytic, Acute
  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
Daunorubicin
Given IV
Cytarabine
Given IV
Clofarabine
Given IV
Decitabine
Given IV
Other:
Observation
Undergo clinical observation
Procedure:
Allogeneic hematopoietic stem cell transplantation
Patients with an HLA-identical donor proceed to allogeneic stem cell transplantation.

Locations

Country Name City State
India Mayo Clinic Methodist Hospital Nagpur
Israel Rambam Medical Center Haifa
Israel Shaare Zedek Medical Center Jerusalem
United States Kapiolani Medical Center at Pali Momi 'Aiea Hawaii
United States Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi 'Aiea Hawaii
United States Akron General Medical Center Akron Ohio
United States Summa Akron City Hospital Akron Ohio
United States Lehigh Valley Hospital Allentown Pennsylvania
United States Saint Anthony's Health Alton Illinois
United States McFarland Clinic Ames Iowa
United States AnMed Health Cancer Center Anderson South Carolina
United States Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor Michigan
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Atlanta Regional CCOP Atlanta Georgia
United States Northside Hospital Atlanta Georgia
United States Piedmont Hospital Atlanta Georgia
United States Saint Joseph's Hospital of Atlanta Atlanta Georgia
United States Georgia Regents University Augusta Georgia
United States Harold Alfond Center for Cancer Care Augusta Maine
United States The Medical Center of Aurora Aurora Colorado
United States Well Star Cobb Hospital Austell Georgia
United States Johns Hopkins University Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Summa Barberton Hospital Barberton Ohio
United States Ochsner Clinic Foundation-Baton Rouge Baton Rouge Louisiana
United States Bronson Battle Creek Battle Creek Michigan
United States Saint Francis Hospital and Health Centers Beech Grove Indiana
United States Sanford Clinic North-Bemidgi Bemidji Minnesota
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Mecosta County Medical Center Big Rapids Michigan
United States Billings Clinic Billings Montana
United States Hematology-Oncology Centers of the Northern Rockies PC Billings Montana
United States Montana Cancer Consortium CCOP Billings Montana
United States Saint Vincent Healthcare Billings Montana
United States University of Alabama at Birmingham Birmingham Alabama
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Joseph Medical Center Bloomington Illinois
United States Saint Alphonsus Regional Medical Center Boise Idaho
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Tufts Medical Center Boston Massachusetts
United States Boulder Community Hospital Boulder Colorado
United States Bozeman Deaconess Cancer Center Bozeman Montana
United States Bozeman Deaconess Hospital Bozeman Montana
United States Essentia Health Saint Joseph's Medical Center Brainerd Minnesota
United States Caritas Saint Elizabeth's Medical Center Brighton Massachusetts
United States Saint James Community Hospital and Cancer Treatment Center Butte Montana
United States Cooper Hospital University Medical Center Camden New Jersey
United States Aultman Health Foundation Canton Ohio
United States Graham Hospital Association Canton Illinois
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Memorial Hospital Carthage Illinois
United States Rocky Mountain Oncology Casper Wyoming
United States West Virginia University Charleston Charleston West Virginia
United States Erlanger Medical Center Chattanooga Tennessee
United States Hematology and Oncology Associates Chicago Illinois
United States Mount Sinai Hospital Medical Center Chicago Illinois
United States Northwestern University Chicago Illinois
United States University of Illinois Chicago Illinois
United States The Jewish Hospital Cincinnati Ohio
United States Clackamas Radiation Oncology Center Clackamas Oregon
United States Case Western Reserve University Cleveland Ohio
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States John B Amos Cancer Center Columbus Georgia
United States Geisinger Medical Center Danville Pennsylvania
United States Dayton CCOP Dayton Ohio
United States Good Samaritan Hospital - Dayton Dayton Ohio
United States Grandview Hospital Dayton Ohio
United States Miami Valley Hospital Dayton Ohio
United States Samaritan North Health Center Dayton Ohio
United States Oakwood Hospital Dearborn Michigan
United States Decatur Memorial Hospital Decatur Illinois
United States Dekalb Medical Center Decatur Georgia
United States Colorado Cancer Research Program CCOP Denver Colorado
United States Exempla Saint Joseph Hospital Denver Colorado
United States Porter Adventist Hospital Denver Colorado
United States Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado
United States Rose Medical Center Denver Colorado
United States Saint Anthony Central Hospital Denver Colorado
United States Saint John Hospital and Medical Center Detroit Michigan
United States Wayne State University Detroit Michigan
United States Essentia Health Duluth Clinic CCOP Duluth Minnesota
United States Essentia Health Saint Mary's Medical Center Duluth Minnesota
United States Miller-Dwan Hospital Duluth Minnesota
United States Union Hospital of Cecil County Elkton Maryland
United States Swedish Medical Center Englewood Colorado
United States Eureka Hospital Eureka Illinois
United States Illinois CancerCare-Eureka Eureka Illinois
United States Roger Maris Cancer Center Fargo North Dakota
United States Sanford Clinic North-Fargo Fargo North Dakota
United States Sanford Medical Center-Fargo Fargo North Dakota
United States Piedmont Fayette Hospital Fayetteville Georgia
United States Lake Region Healthcare Corporation-Cancer Care Fergus Falls Minnesota
United States Blanchard Valley Hospital Findlay Ohio
United States Genesys Hurley Cancer Institute Flint Michigan
United States Genesys Regional Medical Center-West Flint Campus Flint Michigan
United States Hurley Medical Center Flint Michigan
United States Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne Indiana
United States Atrium Medical Center-Middletown Regional Hospital Franklin Ohio
United States University of Florida Gainesville Florida
United States Illinois CancerCare Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States Genesys Regional Medical Center Grand Blanc Michigan
United States Grand Rapids Clinical Oncology Program Grand Rapids Michigan
United States Saint Mary's Health Care Grand Rapids Michigan
United States Spectrum Health at Butterworth Campus Grand Rapids Michigan
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Great Falls Clinic Great Falls Montana
United States North Colorado Medical Center Greeley Colorado
United States Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin
United States Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin
United States Saint Mary's Hospital Green Bay Wisconsin
United States Saint Vincent Hospital Green Bay Wisconsin
United States Saint Francis Hospital Greenville South Carolina
United States Wayne Hospital Greenville Ohio
United States Saint Francis Hospital and Medical Center Hartford Connecticut
United States Illinois CancerCare-Havana Havana Illinois
United States Mason District Hospital Havana Illinois
United States Northern Montana Hospital Havre Montana
United States Geisinger Medical Center-Cancer Center Hazelton Hazleton Pennsylvania
United States Saint Peter's Community Hospital Helena Montana
United States Park Ridge Hospital Breast Health Center Hendersonville North Carolina
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois
United States Hinsdale Hematology Oncology Associates Incorporated Hinsdale Illinois
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Kuakini Medical Center Honolulu Hawaii
United States Oncare Hawaii Inc-Kuakini Honolulu Hawaii
United States Oncare Hawaii Inc-POB II Honolulu Hawaii
United States OnCare Hawaii-Liliha Honolulu Hawaii
United States Queen's Medical Center Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States University of Hawaii Honolulu Hawaii
United States Franciscan St. Francis Health Indianapolis Indiana
United States Allegiance Health Jackson Michigan
United States Jackson-Madison County General Hospital Jackson Tennessee
United States University of Mississippi Medical Center Jackson Mississippi
United States Mayo Clinic in Florida Jacksonville Florida
United States Castle Medical Center Kailua Hawaii
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Glacier Oncology PLLC Kalispell Montana
United States Kalispell Medical Oncology Kalispell Montana
United States Kalispell Regional Medical Center Kalispell Montana
United States Presence Saint Mary's Hospital Kankakee Illinois
United States Kettering Medical Center Kettering Ohio
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Kinston Medical Specialists PA Kinston North Carolina
United States Gundersen Lutheran La Crosse Wisconsin
United States Carolina Blood and Cancer Care Associates PA-Lancaster Lancaster South Carolina
United States Sparrow Hospital Lansing Michigan
United States Nevada Cancer Research Foundation CCOP Las Vegas Nevada
United States Gwinnett Medical Center Lawrenceville Georgia
United States Beebe Medical Center Lewes Delaware
United States Lewistown Hospital Lewistown Pennsylvania
United States University of Kentucky Lexington Kentucky
United States North Shore Hematology Oncology Libertyville Illinois
United States Wilcox Memorial Hospital and Kauai Medical Clinic Lihue Hawaii
United States Saint Rita's Medical Center Lima Ohio
United States Littleton Adventist Hospital Littleton Colorado
United States Saint Mary Mercy Hospital Livonia Michigan
United States Sky Ridge Medical Center Lone Tree Colorado
United States Longmont United Hospital Longmont Colorado
United States Norton Health Care Pavilion - Downtown Louisville Kentucky
United States McKee Medical Center Loveland Colorado
United States Illinois CancerCare-Macomb Macomb Illinois
United States Mcdonough District Hospital Macomb Illinois
United States University of Wisconsin Hospital and Clinics Madison Wisconsin
United States Holy Family Memorial Hospital Manitowoc Wisconsin
United States Wellstar Kennestone Hospital Marietta Georgia
United States Bay Area Medical Center Marinette Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin
United States Providence Milwaukie Hospital Milwaukie Oregon
United States Winthrop University Hospital Mineola New York
United States Montana Cancer Specialists Missoula Montana
United States Saint Patrick Hospital - Community Hospital Missoula Montana
United States Holy Family Medical Center Monmouth Illinois
United States Illinois CancerCare-Monmouth Monmouth Illinois
United States West Virginia University Morgantown West Virginia
United States D N Greenwald Center Mukwonago Wisconsin
United States Mercy Health Partners-Mercy Campus Muskegon Michigan
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States The Hospital of Central Connecticut New Britain Connecticut
United States Ochsner Baptist Medical Center New Orleans Louisiana
United States Ochsner Clinic Foundation New Orleans Louisiana
United States Memorial Sloan Kettering Cancer Center New York New York
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States Providence Newberg Medical Center Newberg Oregon
United States Illinois Cancer Specialists-Niles Niles Illinois
United States Bromenn Regional Medical Center Normal Illinois
United States Community Cancer Center Foundation Normal Illinois
United States Illinois CancerCare-Community Cancer Center Normal Illinois
United States Oconomowoc Memorial Hospital-ProHealth Care Inc Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Providence Willamette Falls Medical Center Oregon City Oregon
United States Florida Hospital Orlando Florida
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Ottawa Regional Hospital and Healthcare Center Ottawa Illinois
United States Parker Adventist Hospital Parker Colorado
United States Illinois CancerCare-Pekin Pekin Illinois
United States Pekin Cancer Treatment Center Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Illinois Oncology Research Association CCOP Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States Proctor Hospital Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Illinois Valley Hospital Peru Illinois
United States Abramson Cancer Center of The University of Pennsylvania Philadelphia Pennsylvania
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Saint Joseph Mercy Port Huron Port Huron Michigan
United States Columbia River Oncology Program Portland Oregon
United States Providence Portland Medical Center Portland Oregon
United States Providence Saint Vincent Medical Center Portland Oregon
United States Illinois CancerCare-Princeton Princeton Illinois
United States Perry Memorial Hospital Princeton Illinois
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States Spectrum Health Reed City Hospital Reed City Michigan
United States Reid Hospital and Health Care Services Richmond Indiana
United States Southern Regional Medical Center Riverdale Georgia
United States Mayo Clinic Rochester Minnesota
United States University of Rochester Rochester New York
United States Carolina Blood and Cancer Care Associates PA Rock Hill South Carolina
United States Swedish American Hospital Rockford Illinois
United States Harbin Clinic Medical Oncology and Clinical Research Rome Georgia
United States Saint Mary's of Michigan Saginaw Michigan
United States Saint John's Mercy Medical Center Saint Louis Missouri
United States Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri
United States Saint Louis University Hospital Saint Louis Missouri
United States Saint Louis-Cape Girardeau CCOP Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Mayo Clinic in Arizona Scottsdale Arizona
United States Saint Nicholas Hospital Sheboygan Wisconsin
United States Welch Cancer Center Sheridan Wyoming
United States Mercy Medical Center-Sioux City Sioux City Iowa
United States Saint Luke's Regional Medical Center Sioux City Iowa
United States Siouxland Hematology Oncology Associates Sioux City Iowa
United States Medical X-Ray Center Sioux Falls South Dakota
United States Sanford Cancer Center-Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Hematology Oncology Associates of Illinois - Skokie Skokie Illinois
United States Providence Hospital Southfield Michigan
United States Spartanburg Regional Medical Center Spartanburg South Carolina
United States Upstate Carolina CCOP Spartanburg South Carolina
United States Illinois CancerCare-Spring Valley Spring Valley Illinois
United States Baystate Medical Center Springfield Massachusetts
United States Memorial Medical Center Springfield Illinois
United States Geisinger Medical Group State College Pennsylvania
United States Mount Nittany Medical Center State College Pennsylvania
United States North Suburban Medical Center Thornton Colorado
United States Munson Medical Center Traverse City Michigan
United States Upper Valley Medical Center Troy Ohio
United States Arizona Cancer Center at University Medical Center North Tucson Arizona
United States University of Arizona Health Sciences Center Tucson Arizona
United States Northwest Cancer Specialists Vancouver Washington
United States PeaceHealth Southwest Medical Center Vancouver Washington
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Waukesha Memorial Hospital - ProHealth Care Waukesha Wisconsin
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Exempla Lutheran Medical Center Wheat Ridge Colorado
United States Geisinger Wyoming Valley Wilkes-Barre Pennsylvania
United States Clinton Memorial Hospital Wilmington Ohio
United States Greene Memorial Hospital Xenia Ohio
United States York Hospital York Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
ECOG-ACRIN Cancer Research Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  India,  Israel, 

Outcome

Type Measure Description Time frame Safety issue
Other Expression and Methylation Profiling DNA methylation profiling and gene expression are evaluated using peripheral blood samples collected at baseline of the maintenance treatment (prior to 2nd randomization). These are to be compared between patients with decitabine and patients on observation. Baseline of maintenance treatment
Other Relapse After Decitabine Maintenance by Epigenetic Signature of Normal Bone Marrow To examine the epigenetic profiles of remission marrow among patients randomized to observation vs. decitabine to determine whether epigenetic signature of apparently morphologically normal bone marrow is predictive of relapse or response to decitabine maintenance.
Relapse following complete remission is defined as:
Peripheral Blood Counts
Reappearance of blasts in the blood
Bone Marrow Aspirate and Biopsy
Presence of > 5% blasts, not attributable to another cause (e.g., bone marrow regeneration).
If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed = 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
Assessed every 3 months for 4 years and then every 6 months for 1 year
Other Complete Remission Rate by ABC-transporter P-glycoprotein (Pgp) Patients with all the following are considered as having a complete remission.
Peripheral Blood Counts
Neutrophil count > 1.0 x 109 /L
Platelet count = 100 x 109 /L
Reduced hemoglobin concentration or hematocrit has no bearing on remission status
Leukemic blasts must not be present in the peripheral blood
Bone Marrow Aspirate and Biopsy
Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines
< 5% blasts by morphologic review
Auer rods must not be detectable
Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present
The proportion of patients with complete remission will be compared between patients who overexpress Pgp and patients who do not overexpress Pgp.
Assessed every 3 months for 4 years and then every 6 months for 1 year
Other To Assess the Intensity of Expression of CXCR4 on Diagnostic Leukemia Cells and to Correlate This Parameter With Other Established Prognostic Factors Expression of CXCR4 will be assessed in this study by flow cytometric assay. The associations between the expression level and other prognostic factors in patients receiving induction treatment will be evaluated. Baseline
Other The Association Between Somatic Mutations and Relapse Relapse following complete remission is defined as:
Peripheral Blood Counts
Reappearance of blasts in the blood
Bone Marrow Aspirate and Biopsy
Presence of > 5% blasts, not attributable to another cause (e.g., bone marrow regeneration).
If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed = 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.
Assessed every 3 months for 4 years and then every 6 months for 1 year
Other Overall Survival by Patient Characteristics and Lifestyle Overall survival is defined as time from randomization to death or date last known alive. The associations between overall survival and smoking status, obesity, regular acetaminophen use, regular aspirin use, benzene exposure, living in a rural/farm environment and some other underlying exposures and lifestyle factors will be evaluated. Assessed every 3 months for 4 years and then every 6 months for 1 year
Other Copy Number Changes Using Array Comparative Genomic Hybridization (CGH) by Patient Characteristics Copy number changes will be tested based on array CGH technology. The associations between copy number changes and acute myeloid leukemia patient characteristics will be evaluated. Baseline
Other Quality of Life (QOL) Assessed by Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) QOL will be assessed using the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu). This instrument combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific subscale. The total score of FACT-Leu ranges between 0 and 176. Higher score indicates better QOL. Assessed at baseline, 14 days after 1st induction treatment, prior to consolidation therapy (day 35-36), prior to maintenance treatment, end of maintenance treatment
Other Change in Health-related QOL Over Time QOL will be assessed using the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu). This instrument combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific subscale. The total score of FACT-Leu ranges between 0 and 176. Higher score indicates better QOL.
Changes in QOL will be calculated by subtracting baseline QOL score from follow-up QOL score.
Assessed at baseline, 14 days after 1st induction treatment, prior to consolidation therapy (day 35-36), prior to maintenance treatment, end of maintenance treatment
Other Patient Function Assessed by Functional Assessment of Cancer Therapy - General (FACT-G) QOL will be assessed using the Functional Assessment of Cancer Therapy - General (FACT-G). FACT-G includes 4 subscales, physical well-being (score range: 0-28), social/family well-being (score range: 0-28), emotional well-being (score range: 0-24), and functional well-being (score range: 0-28). The total score of FACT-G ranges between 0 and 108. Higher score indicates better QOL. Assessed at baseline
Other Change in QOL Post Transplant From Baseline For those patients who go to allo transplant, the FACT-Leu and the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) instruments will be administered at the beginning of the conditioning regimen and 100 days (+14 days) post transplant.
FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific subscale. The total score of FACT-Leu ranges between 0 and 176. Higher score indicates better QOL.
FACIT-Fatigue has 13 items and the total score ranges between 0 and 52. Higher score indicates better QOL.
Changes in QOL will be calculated by subtracting baseline QOL score from follow-up QOL score.
Assessed prior to transplant and 100 days after transplant
Other Baseline QOL Scores by Treatment Completion Status The associations between baseline QOL scores and the ability to finish treatment will be evaluated. Baseline QOL will be assessed using the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) and the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue).
FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific subscale. The total score of FACT-Leu ranges between 0 and 176. Higher score indicates better QOL.
FACIT-Fatigue has 13 items and the total score ranges between 0 and 52. Higher score indicates better QOL.
Assessed at baseline
Primary Overall Survival Overall survival is defined as the time from randomization to death or date last known alive. Assessed every 3 months for 4 years and then every 6 months for 1 year
Secondary Proportion of Patients With Complete Remission Patients are required to have all of the following to be considered as having a completion remission (CR).
Peripheral Blood Counts
Neutrophil count > 1.0 x 10^9 /L
Platelet count = 100 x 10^9 /L
Reduced hemoglobin concentration or hematocrit has no bearing on remission status
Leukemic blasts must not be present in the peripheral blood
Bone Marrow Aspirate and Biopsy
Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines
< 5% blasts by morphologic review
Auer rods must not be detectable
Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present
Assessed every 3 months for 4 years and then every 6 months for 1 year
Secondary Overall Survival by Donor Status Overall survival is defined as time between achieving leukemia-free state after induction therapy to death from any cause or date last known alive. The association between overall survival and donor status was evaluated regardless of assigned treatment arms. Patients with transplant donor information (either had donor or did not have a donor) reported after achieving CR/Cri/leukemia-free state post induction therapy were included in this analysis. Assessed every 3 months for 4 years and then every 6 months for 1 year
Secondary Disease-free Survival for Maintenance DFS for maintenance comparison is defined as the time from maintenance randomization until relapse or death of any cause. The censored follow-up time for patients without relapse and death information is the date of last contact. Only patients who remained in CR or CRi after completion of consolidation therapy that were randomized to either observation or decitabine in the maintenance Step were included in this analysis. Assessed every 3 months for 4 years and then every 6 months for 1 year
See also
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