Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin &Amp; Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Followed by Decitabine Maintenance vs. Observation in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age >/= 60 Years)

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
• 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
• 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

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