Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin & 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)
- To compare the overall survival of older patients with newly diagnosed acute myeloid
leukemia (AML) treated with clofarabine as induction therapy and consolidation therapy
vs standard daunorubicin hydrochloride and cytarabine.
- To evaluate complete remission (CR) rates, duration of remission, and
toxicity/treatment-related mortality of patients treated with these regimens.
- To evaluate the feasibility of consolidation therapy with reduced-intensity
conditioning and allogeneic hematopoietic stem cell transplantation from HLA-identical
donors, in terms of the incidence of successful engraftment, acute and chronic
graft-vs-host disease, and transplant-related mortality in select patients age 60-69
years who achieve a response to induction therapy.
- To determine the impact of reduced-intensity conditioning and allogeneic stem cell
transplantation on overall survival of select patients.
- To compare the duration of remission and disease-free survival of patients in CR
following completion of consolidation therapy who are subsequently randomized to
receive decitabine as maintenance therapy vs observation.
- To perform expression and methylation profiling in patients treated with decitabine as
maintenance therapy and to correlate their integrated epigenetic signatures with
response to decitabine.
- To examine the epigenetic profiles of remission marrow in patients randomized to
receive decitabine as maintenance therapy vs observation to determine whether
epigenetic signatures of apparently morphologically normal bone marrow is predictive of
relapse or response to decitabine.
- To explore the possible association of response to clofarabine with nucleoside
transporters hENT1, hCNT3, and ABC-transporter P-glycoprotein.
- To assess the intensity of expression of CXCR4 on diagnostic leukemia cells and to
correlate this parameter with other established prognostic factors.
- To assess the entire spectrum of somatic mutations and affected pathways at diagnosis
of AML and elucidate the association between gene mutation and outcome.
- To compare health-related quality of life (QOL) (physical, functional,
leukemia-specific well-being) and fatigue in patients treated with clofarabine vs
standard induction therapy.
- To measure the change in health-related QOL that occurs over time.
- To comprehensively assess patient function at the time of study enrollment.
- To determine if components of a comprehensive geriatric assessment or QOL scale predict
ability to complete treatment for AML.
- To describe the impact of transplantation on QOL in patients with AML over 60 years of
OUTLINE: This is a multicenter study. Patients are stratified according to age (60-69 years
vs ≥ 70 years), , disease type (secondary vs de novo), therapy-related AML (yes vs no), and
antecedent hematologic disorder (yes vs no).
- Induction therapy: Patients are randomized to 1 of 2 treatment arms.
- Arm I (standard therapy): Patients receive daunorubicin hydrochloride IV over
10-15 minutes on days 1-3 and cytarabine 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 II: Patients receive clofarabine 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 incomplete (CRi) after induction
therapy proceed to consolidation therapy. 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. Patients undergoing second induction
who do not achieve CR by day 56 of the start of re-induction are taken off protocol.
- 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
- Arm I (standard therapy): Patients receive cytarabine IV over 1 hour once or twice
daily on days 1-6. Treatment repeats every 4-6 weeks for 2 courses.
- Arm II: Patients receive clofarabine 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 proceed to maintenance
- Maintenance therapy: Beginning within 60 days after completion of consolidation
therapy, patients receive maintenance therapy and are randomized to 1 of 2 arms.
- Arm I: Patients undergo observation monthly for 12 months.
- Arm II: Patients receive decitabine 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:
Patients begin reduced-intensity conditioning 30-90 days after the initiation of
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on
days -7 to -3, busulfan IV over 2 hours every 6 hours on days -4 and -3 (for a
total of 8 doses), and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.
- Transplantation: Patients undergo allogeneic peripheral blood stem cell
transplantation on day 0.
Patients complete quality-of-life questionnaires periodically, including health-related
quality of life, physical and functional well-being, and fatigue questionnaires.
Peripheral blood, bone marrow, and karyotype samples are collected periodically for
cytogenetic analysis and other correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for ≥ 5 years.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
James M. Foran, MD, FRCPC
|Mayo Clinic Scottsdale||Scottsdale, Arizona 85259|
|Mayo Clinic - Jacksonville||Jacksonville, Florida 32224|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Cardinal Bernardin Cancer Center at Loyola University Medical Center||Maywood, Illinois 60153-5500|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - Illinois Oncology Research Association||Peoria, Illinois 61602|
|George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus||New Britain, Connecticut 06050|
|Mercy Medical Center - Sioux City||Sioux City, Iowa 51104|
|Siouxland Hematology-Oncology Associates, LLP||Sioux City, Iowa 51101|
|St. Luke's Regional Medical Center||Sioux City, Iowa 51104|
|Baystate Regional Cancer Program at D'Amour Center for Cancer Care||Springfield, Massachusetts 01199|
|Bronson Methodist Hospital||Kalamazoo, Michigan 49007|
|West Michigan Cancer Center||Kalamazoo, Michigan 49007-3731|
|Borgess Medical Center||Kalamazooaa, Michigan 49001|
|MeritCare Bemidji||Bemidji, Minnesota 56601|
|Duluth Clinic Cancer Center - Duluth||Duluth, Minnesota 55805-1983|
|CCOP - Duluth||Duluth, Minnesota 55805|
|Miller - Dwan Medical Center||Duluth, Minnesota 55805|
|MeritCare Broadway||Fargo, North Dakota 58122|
|CCOP - MeritCare Hospital||Fargo, North Dakota 58122|
|Aultman Cancer Center at Aultman Hospital||Canton, Ohio 44710-1799|
|Jewish Hospital Cancer Center||Cincinnati, Ohio 45236|
|St. Rita's Medical Center||Lima, Ohio 45801|
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Geisinger Medical Group - Scenery Park||State College, Pennsylvania 16801|
|Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center||Wilkes-Barre, Pennsylvania 18711|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792-6164|
|Medical College of Wisconsin Cancer Center||Milwaukee, Wisconsin 53226|
|Methodist Medical Center of Illinois||Peoria, Illinois 61636|
|CCOP - Montana Cancer Consortium||Billings, Montana 59101|
|CCOP - Dayton||Kettering, Ohio 45429|
|CCOP - Grand Rapids||Grand Rapids, Michigan 49503|
|CCOP - St. Louis-Cape Girardeau||Saint Louis, Missouri 63141|
|Waukesha Memorial Hospital Regional Cancer Center||Waukesha, Wisconsin 53188|
|Florida Hospital Cancer Institute at Florida Hospital Orlando||Orlando, Florida 32803-1273|
|Mary Babb Randolph Cancer Center at West Virginia University Hospitals||Morgantown, West Virginia 26506|
|Lewistown Hospital||Lewistown, Pennsylvania 17044|
|Mount Nittany Medical Center||State College, Pennsylvania 16803|
|Saint Anthony's Hospital at Saint Anthony's Health Center||Alton, Illinois 62002|
|Good Samaritan Regional Health Center||Mt. Vernon, Illinois 62864|
|Battle Creek Health System Cancer Care Center||Battle Creek, Michigan 49017|
|Munson Medical Center||Traverse City, Michigan 49684|
|David C. Pratt Cancer Center at St. John's Mercy||St. Louis, Missouri 63141|
|Hematology-Oncology Centers of the Northern Rockies - Billings||Billings, Montana 59101|
|St. Peter's Hospital||Helena, Montana 59601|
|Kalispell Regional Medical Center||Kalispell, Montana 59901|
|Glacier Oncology, PLLC||Kalispell, Montana 59901|
|Montana Cancer Center at St. Patrick Hospital and Health Sciences Center||Missoula, Montana 59802|
|MBCCOP - Medical College of Georgia Cancer Center||Augusta, Georgia 30912-3730|
|Swedish-American Regional Cancer Center||Rockford, Illinois 61104-2315|
|Butterworth Hospital at Spectrum Health||Grand Rapids, Michigan 49503-2560|
|CCOP - Nevada Cancer Research Foundation||Las Vegas, Nevada 89109-2306|
|Oklahoma University Cancer Institute||Oklahoma City, Oklahoma 73104|
|Geisinger Cancer Institute at Geisinger Health||Danville, Pennsylvania 17822-0001|
|West Virginia University Health Sciences Center - Charleston||Charleston, West Virginia 25302|
|Gundersen Lutheran Center for Cancer and Blood||La Crosse, Wisconsin 54601|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Decatur Memorial Hospital Cancer Care Institute||Decatur, Illinois 62526|
|Hematology Oncology Associates - Skokie||Skokie, Illinois 60076|
|Joan Karnell Cancer Center at Pennsylvania Hospital||Philadelphia, Pennsylvania 19107|
|St. Joseph Medical Center||Bloomington, Illinois 61701|
|Graham Hospital||Canton, Illinois 61520|
|Memorial Hospital||Carthage, Illinois 62321|
|Hematology and Oncology Associates||Chicago, Illinois 60611|
|Eureka Community Hospital||Eureka, Illinois 61530|
|Mason District Hospital||Havana, Illinois 62644|
|North Shore Oncology and Hematology Associates, Limited - Libertyville||Libertyville, Illinois 60048|
|McDonough District Hospital||Macomb, Illinois 61455|
|BroMenn Regional Medical Center||Normal, Illinois 61761|
|Community Cancer Center||Normal, Illinois 61761|
|Community Hospital of Ottawa||Ottawa, Illinois 61350|
|Oncology Hematology Associates of Central Illinois, PC - Ottawa||Ottawa, Illinois 61350|
|Cancer Treatment Center at Pekin Hospital||Pekin, Illinois 61554|
|Oncology Hematology Associates of Central Illinois, PC - Peoria||Peoria, Illinois 61615|
|OSF St. Francis Medical Center||Peoria, Illinois 61637|
|Proctor Hospital||Peoria, Illinois 61614|
|Illinois Valley Community Hospital||Peru, Illinois 61354|
|Perry Memorial Hospital||Princeton, Illinois 61356|
|St. Francis Hospital and Health Centers - Beech Grove Campus||Beech Grove, Indiana 46107|
|Fort Wayne Medical Oncology and Hematology||Fort Wayne, Indiana 46815|
|Mecosta County Medical Center||Big Rapids, Michigan 49307|
|St. Joseph's Medical Center||Brainerd, Minnesota 56401|
|Saint Francis Medical Center||Cape Girardeau, Missouri 63701|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Samaritan North Cancer Care Center||Dayton, Ohio 45415|
|Grandview Hospital||Dayton, Ohio 45405|
|David L. Rike Cancer Center at Miami Valley Hospital||Dayton, Ohio 45409|
|Good Samaritan Hospital||Dayton, Ohio 45406|
|Blanchard Valley Medical Associates||Findlay, Ohio 45840|
|Charles F. Kettering Memorial Hospital||Kettering, Ohio 45429|
|Middletown Regional Hospital||Middletown, Ohio 45044|
|UVMC Cancer Care Center at Upper Valley Medical Center||Troy, Ohio 45373-1300|
|Ruth G. McMillan Cancer Center at Greene Memorial Hospital||Xenia, Ohio 45385|
|Welch Cancer Center at Sheridan Memorial Hospital||Sheridan, Wyoming 82801|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|Kellogg Cancer Care Center||Highland Park, Illinois 60035|
|Cancer Care and Hematology Specialists of Chicagoland - Niles||Niles, Illinois 60714|
|Reid Hospital & Health Care Services||Richmond, Indiana 47374|
|McFarland Clinic, PC||Ames, Iowa 50010|
|Billings Clinic - Downtown||Billings, Montana 59107-7000|
|Bozeman Deaconess Cancer Center||Bozeman, Montana 59715|
|St. James Healthcare Cancer Care||Butte, Montana 59701|
|Great Falls Clinic - Main Facility||Great Falls, Montana 59405|
|Sletten Cancer Institute at Benefis Healthcare||Great Falls, Montana 59405|
|Northern Montana Hospital||Havre, Montana 59501|
|Kalispell Medical Oncology at KRMC||Kalispell, Montana 59901|
|Summa Center for Cancer Care at Akron City Hospital||Akron, Ohio 44309-2090|
|Barberton Citizens Hospital||Barberton, Ohio 44203|
|Wayne Hospital||Greenville, Ohio 45331|
|Geisinger Hazleton Cancer Center||Hazleton, Pennsylvania 18201|
|Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033-0850|
|Hematology and Oncology Associates of Northeastern Pennsylvania||Scranton, Pennsylvania 18510|
|York Cancer Center at Apple Hill Medical Center||York, Pennsylvania 17405|
|Regional Cancer Center at Memorial Medical Center||Springfield, Illinois 62781-0001|
|Regional Cancer Center at Oconomowoc Memorial Hospital||Oconomowoc, Wisconsin 53066|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Kinston Medical Specialists||Kinston, North Carolina 28501|
|West Tennessee Cancer Center at Jackson-Madison County General Hospital||Jackson, Tennessee 38301|
|Lacks Cancer Center at Saint Mary's Health Care||Grand Rapids, Michigan 49503|
|Galesburg Clinic, PC||Galesburg, Illinois 61401|
|St. Vincent Healthcare Cancer Care Services||Billings, Montana 59101|
|Midwest Hematology Oncology Group, Incorporated||Saint Louis, Missouri 63109|
|Illinois CancerCare - Bloomington||Bloomington%, Illinois 61701|
|Illinois CancerCare - Canton||Canton, Illinois 61520|
|Illinois CancerCare - Carthage||Carthage, Illinois 62321|
|Illinois CancerCare - Eureka||Eureka, Illinois 61530|
|Illinois CancerCare - Galesburg||Galesburg, Illinois 61401|
|Illinois CancerCare - Havana||Havana, Illinois 62644|
|Illinois CancerCare - Kewanee Clinic||Kewanee, Illinois 61443|
|Illinois CancerCare - Macomb||Macomb, Illinois 61455|
|OSF Holy Family Medical Center||Monmouth, Illinois 61462|
|Illinois CancerCare - Monmouth||Monmouth, Illinois 61462|
|Illinois CancerCare - Community Cancer Center||Normal, Illinois 61761|
|Illinois CancerCare - Pekin||Pekin, Illinois 61603|
|Illinois CancerCare - Peru||Peru, Illinois 61354|
|Illinois CancerCare - Princeton||Princeton, Illinois 61356|
|Illinois CancerCare - Spring Valley||Spring Valley, Illinois 61362|
|Mercy General Health Partners||Muskegon, Michigan 49443|
|Provena St. Mary's Regional Cancer Center - Kankakee||Kankakee, Illinois 60901|
|Tufts Medical Center Cancer Center||Boston, Massachusetts 02111|
|Roger Maris Cancer Center at MeritCare Hospital||Fargo, North Dakota 58122|
|D.N. Greenwald Center||Mukwonago, Wisconsin 53149|