Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome focused on measuring acute myeloid leukemia, Clofarabine, Daunorubicin, Cytarabine, Decitabine
Eligibility Criteria
Inclusion Criteria:
- Sexually active males must be strongly advised to use an accepted and effective method of contraception
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< grade 1
Total bilirubin =< grade 1
- Note: If total bilirubin is 2 to 3 mg/dL, but direct bilirubin is normal, then the patient will be considered eligible
- Patient must not have a concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS])
- Patient must not have an active, uncontrolled infection
- ADDITIONAL INDUCTION ELIGIBILITY CRITERIA:
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
- NOTE: patients must be registered to E3903 (Ancillary Laboratory Protocol for the Collection of Diagnostic Material on Patients Considered for Eastern Cooperative Oncology Group (ECOG) Treatment Trials for Leukemia or Related Hematologic Disorders) and must undergo eligibility testing for the study by multiparameter flow cytometry
- NOTE: Southwest Oncology Group (SWOG)/Cancer Trials Support Unit (CTSU) institutions: E3903 is not open at the CTSU; therefore, baseline submissions must be submitted on E2906
- ECOG performance status (PS) 0-3 (restricted to ECOG PS 0-2 if >= 70 years of age)
- Patients with 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 will be excluded
- Patients must not have blastic transformation of chronic myelogenous leukemia
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
- NOTE: Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine is excluded
- Patients may not have received prior chemotherapy for AML with the exception of hydroxyurea for increased blast count or leukapheresis for leukocytosis
- 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; those with documented CNS involvement will be excluded
Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (>10^9/l) from peripheral blood; this must be done via E3903
- NOTE: SWOG/CTSU institutions: E3903 is not open at the CTSU; therefore, baseline submissions must be submitted on E2906
- Patients who have received previous treatment for antecedent hematological disorders (AHD) with 5-azacitidine, decitabine, or low dose cytarabine will be excluded
- Patients with known human immunodeficiency virus (HIV) infection are excluded
- 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; this must be done via E2906
- NOTE: SWOG/CTSU institutions: E3903 is not open at the CTSU; therefore, baseline submissions must be submitted on E2906
- CONSOLIDATION CRITERIA:
- NOTE: All patients achieving 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
- Patients must have an 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
- MAINTENANCE CRITERIA:
- 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
- Patients must have an 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
- ALLOGENEIC TRANSPLANTATION:
- Patients must be > 30 days and < 90 days from the start of induction or re-induction chemotherapy, or > 30 days and < 90 days of recovery from consolidation cycle 1 (if received), and must have achieved a response to induction therapy (CR, CRi, or "morphologic disease-free state", documented > 27 days after start of most-recent chemotherapy)
- 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
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
- No known hypersensitivity to Escherichia (E.) coli-derived products
- No human immunodeficiency virus (HIV) infection; patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies
- Creatinine =< grade 1
Bilirubin =< grade 1
- If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be considered eligible
- AST =< grade 1
Sites / Locations
- University of Alabama at Birmingham
- Mayo Clinic in Arizona
- Arizona Cancer Center at University Medical Center North
- University of Arizona Health Sciences Center
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Saint Anthony Central Hospital
- Porter Adventist Hospital
- Exempla Saint Joseph Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- Rose Medical Center
- Colorado Cancer Research Program CCOP
- Swedish Medical Center
- North Colorado Medical Center
- Littleton Adventist Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Parker Adventist Hospital
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- Exempla Lutheran Medical Center
- Saint Francis Hospital and Medical Center
- The Hospital of Central Connecticut
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- University of Florida
- Mayo Clinic in Florida
- Florida Hospital
- Piedmont Hospital
- Atlanta Regional CCOP
- Northside Hospital
- Saint Joseph's Hospital of Atlanta
- Georgia Regents University
- Well Star Cobb Hospital
- John B Amos Cancer Center
- Dekalb Medical Center
- Piedmont Fayette Hospital
- Gwinnett Medical Center
- Wellstar Kennestone Hospital
- Southern Regional Medical Center
- Harbin Clinic Medical Oncology and Clinical Research
- Kapiolani Medical Center at Pali Momi
- Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi
- Oncare Hawaii Inc-POB II
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii
- OnCare Hawaii-Liliha
- Kuakini Medical Center
- Oncare Hawaii Inc-Kuakini
- Kapiolani Medical Center for Women and Children
- Castle Medical Center
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Regional Medical Center
- Saint Anthony's Health
- Illinois CancerCare-Bloomington
- Saint Joseph Medical Center
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Mount Sinai Hospital Medical Center
- Hematology and Oncology Associates
- Northwestern University
- University of Illinois
- Decatur Memorial Hospital
- Eureka Hospital
- Illinois CancerCare-Eureka
- Illinois CancerCare Galesburg
- Western Illinois Cancer Treatment Center
- Illinois CancerCare-Havana
- Mason District Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Hinsdale Hematology Oncology Associates Incorporated
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- North Shore Hematology Oncology
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Loyola University Medical Center
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Community Cancer Center Foundation
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Pekin Cancer Treatment Center
- Illinois CancerCare-Pekin
- Methodist Medical Center of Illinois
- Proctor Hospital
- Illinois CancerCare-Peoria
- Illinois Oncology Research Association CCOP
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- Swedish American Hospital
- Hematology Oncology Associates of Illinois - Skokie
- Illinois CancerCare-Spring Valley
- Memorial Medical Center
- Saint Francis Hospital and Health Centers
- Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
- Franciscan St. Francis Health
- Reid Hospital and Health Care Services
- McFarland Clinic
- Siouxland Hematology Oncology Associates
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- University of Kentucky
- Norton Health Care Pavilion - Downtown
- Ochsner Clinic Foundation-Baton Rouge
- Ochsner Baptist Medical Center
- Ochsner Clinic Foundation
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- Johns Hopkins University
- Walter Reed National Military Medical Center
- Union Hospital of Cecil County
- Tufts Medical Center
- Beth Israel Deaconess Medical Center
- Caritas Saint Elizabeth's Medical Center
- Baystate Medical Center
- Saint Joseph Mercy Hospital
- Michigan Cancer Research Consortium Community Clinical Oncology Program
- Bronson Battle Creek
- Mecosta County Medical Center
- Oakwood Hospital
- Wayne State University
- Saint John Hospital and Medical Center
- Hurley Medical Center
- Genesys Hurley Cancer Institute
- Genesys Regional Medical Center-West Flint Campus
- Genesys Regional Medical Center
- Grand Rapids Clinical Oncology Program
- Saint Mary's Health Care
- Spectrum Health at Butterworth Campus
- Allegiance Health
- Borgess Medical Center
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Mercy Health Partners-Mercy Campus
- Saint Joseph Mercy Oakland
- Saint Joseph Mercy Port Huron
- Spectrum Health Reed City Hospital
- Saint Mary's of Michigan
- Providence Hospital
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Sanford Clinic North-Bemidgi
- Essentia Health Saint Joseph's Medical Center
- Essentia Health Duluth Clinic CCOP
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Mayo Clinic
- University of Mississippi Medical Center
- Saint Francis Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Saint Louis University Hospital
- Washington University School of Medicine
- Saint John's Mercy Medical Center
- Saint Louis-Cape Girardeau CCOP
- Montana Cancer Consortium CCOP
- Saint Vincent Healthcare
- Hematology-Oncology Centers of the Northern Rockies PC
- Billings Clinic
- Bozeman Deaconess Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Nevada Cancer Research Foundation CCOP
- Cooper Hospital University Medical Center
- Winthrop University Hospital
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- Park Ridge Hospital Breast Health Center
- Kinston Medical Specialists PA
- Roger Maris Cancer Center
- Sanford Clinic North-Fargo
- Sanford Medical Center-Fargo
- Summa Akron City Hospital
- Akron General Medical Center
- Summa Barberton Hospital
- Aultman Health Foundation
- The Jewish Hospital
- Case Western Reserve University
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Dayton CCOP
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Saint Rita's Medical Center
- Upper Valley Medical Center
- Clinton Memorial Hospital
- Greene Memorial Hospital
- University of Oklahoma Health Sciences Center
- Clackamas Radiation Oncology Center
- Providence Milwaukie Hospital
- Providence Newberg Medical Center
- Providence Willamette Falls Medical Center
- Providence Portland Medical Center
- Columbia River Oncology Program
- Providence Saint Vincent Medical Center
- Lehigh Valley Hospital
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazelton
- Penn State Milton S Hershey Medical Center
- Lewistown Hospital
- Abramson Cancer Center of The University of Pennsylvania
- Fox Chase Cancer Center
- Geisinger Medical Group
- Mount Nittany Medical Center
- Geisinger Wyoming Valley
- York Hospital
- AnMed Health Cancer Center
- Saint Francis Hospital
- Carolina Blood and Cancer Care Associates PA-Lancaster
- Carolina Blood and Cancer Care Associates PA
- Spartanburg Regional Medical Center
- Upstate Carolina CCOP
- Sanford Cancer Center-Oncology Clinic
- Medical X-Ray Center
- Sanford USD Medical Center - Sioux Falls
- Erlanger Medical Center
- Jackson-Madison County General Hospital
- Vanderbilt-Ingram Cancer Center
- PeaceHealth Southwest Medical Center
- Northwest Cancer Specialists
- West Virginia University Charleston
- West Virginia University
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Mary's Hospital
- Gundersen Lutheran
- University of Wisconsin Hospital and Clinics
- Holy Family Memorial Hospital
- Bay Area Medical Center
- Froedtert and the Medical College of Wisconsin
- D N Greenwald Center
- Oconomowoc Memorial Hospital-ProHealth Care Inc
- Saint Nicholas Hospital
- Waukesha Memorial Hospital - ProHealth Care
- Aurora Cancer Care-Milwaukee West
- Rocky Mountain Oncology
- Welch Cancer Center
- Mayo Clinic Methodist Hospital
- Rambam Medical Center
- Shaare Zedek Medical Center
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
A (Induction:daunorubicin/cytarabine; consolidation:cytarabine; maintenance:observation/transplant)
B (Induction: clofarabine; Consolidation: clofarabine; Maintenance: decitabine or transplant)
See Detailed Description
See Detailed Description