S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML

A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®) During Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With Gemtuzumab Ozogamicin (Mylotarg®) or No Additional Therapy For Patients Under Age 61 With Previously Untreated De Novo Acute Myeloid Leukemia (AML)

RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop cancer cells from dividing so they stop growing and die. Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with gemtuzumab ozogamicin may kill more cancer cells. It is not yet known whether induction therapy using cytarabine and daunorubicin is more effective with or without gemtuzumab ozogamicin or whether postconsolidation therapy using gemtuzumab ozogamicin is more effective than no additional therapy in treating de novo (first occurrence) acute myeloid leukemia.

PURPOSE: This randomized phase III trial is comparing two different regimens of chemotherapy and monoclonal antibody therapy to see how well they work in treating patients with previously untreated de novo acute myeloid leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: gemtuzumab ozogamicin; Other: observation; Drug: Cytosine arabinoside; Drug: Daunomycin

Detailed Description

OBJECTIVES:

• Compare disease-free survival of patients with previously untreated de novo acute myeloid leukemia treated with induction therapy comprising cytarabine and daunorubicin with vs without gemtuzumab ozogamicin followed by consolidation therapy comprising high-dose cytarabine and post-consolidation therapy comprising gemtuzumab ozogamicin vs no additional therapy.
• Compare the complete remission rate in patients treated with these regimens.
• Compare the frequency and severity of the toxic effects of these regimens in these patients.

Other objectives (if funding allows):

• Determine the prognostic significance of CD33 expression on the response rate in patients receiving gemtuzumab ozogamicin.
• Determine the prognostic significance of FLT3 mutations in these patients before treatment with these regimens.
• Determine the prognostic significance of minimal residual disease in remission specimens from these patients treated with these regimens.
• Determine the prognostic significance of the flow cytometric detection of minimal residual disease in specimens collected from these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified during induction therapy according to age (< 35 years vs ≥ 35 years) and during post-consolidation therapy according to preinduction cytogenetic risk group.

• Induction therapy: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive daunorubicin IV on days 1-3, cytarabine IV continuously on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4. Patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously once daily beginning on day 15 and continuing until blood counts recover.
  • Arm II: Patients receive daunorubicin, cytarabine, and G-CSF or GM-CSF as in arm I.

Patients in both arms undergo bone marrow aspiration and biopsy on day 14 (and on day 19, if applicable) and then proceed to reinduction therapy.

• Reinduction therapy: Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. Patients also receive G-CSF or GM-CSF as in induction therapy.

Patients who achieve A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy.

• Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients who maintain A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status after consolidation therapy proceed to post-consolidation therapy.

• Post-consolidation therapy: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 684 patients (342 per treatment arm) will be accrued for this study within 4.5-5 years.

• Study Type: Interventional
• Enrollment (Actual): 637
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z4
      • University of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Nova Scotia Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario At Kingston General Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Cancer Care Program at Thunder Bay Regional Health Sciences
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrement - Quebec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• Sweden
  • Goteborg, Sweden, 413 45
    • Sahlgrenska University Hospital
  • Huddinge, Sweden, SE-141 86
    • Karolinska University Hospital - Huddinge
  • Linkoping, Sweden, 85
    • University Hospital of Linkoping
  • Lund, Sweden, S-221 00
    • Lund University Hospital
  • Orebro, Sweden, SE-700
    • Orebro University Hospital
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital - Solna
  • Sundsvalls, Sweden, SE-85186
    • Sundsvall Hospital
  • Uppsala, Sweden
    • Uppsala University Hospital
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
  • Arkansas
    • Ft. Smith, Arkansas, United States, 72903
      • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Comprehensive Cancer Center
    • Burlingame, California, United States, 94010
      • Peninsula Medical Center
    • Greenbrae, California, United States, 94904
      • Marin Cancer Institute at Marin General Hospital
    • Greenbrae, California, United States, 94904
      • Sutter Health - Western Division Cancer Research Group
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center - California Campus
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center
  • Florida
    • Lakeland, Florida, United States, 33805
      • Center for Cancer Care and Research at Watson Clinic, LLP
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Cancer Center at Phoebe Putney Memorial Hospital
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
    • Davenport, Iowa, United States, 52803
      • Genesis Regional Cancer Center at Genesis Medical Center
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center Office of Clinical Research
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
    • Baton Rouge, Louisiana, United States, 70806
      • Pennington Cancer Center at Baton Rouge General
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Medical Center of Louisiana - New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Brighton, Massachusetts, United States, 02135-2997
      • Caritas St. Elizabeth's Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49443
      • Mercy General Health Partners
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805-1983
      • Duluth Clinic Cancer Center - Duluth
    • Duluth, Minnesota, United States, 55805
      • Miller - Dwan Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Independence, Missouri, United States, 64050
      • Independence Regional Health Center
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center - Hospital Hill
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64114
      • St. Joseph Medical Center
    • Kansas City, Missouri, United States, 64116
      • Parvin Radiation Oncology
    • Liberty, Missouri, United States, 64068
      • Liberty Hospital
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63109
      • Midwest Hematology Oncology Group, Incorporated
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Center
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Canton, Ohio, United States, 44710-1799
      • Aultman Cancer Center at Aultman Hospital
    • Canton, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Cancer Center at Guthrie Clinic Sayre
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital Cancer Center - Scranton
    • Scranton, Pennsylvania, United States, 18510
      • Hematology and Oncology Associates of Northeastern Pennsylvania
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Florence, South Carolina, United States, 29501
      • McLeod Regional Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • University Hospital - San Antonio
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84103
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405-3004
      • Franciscan Cancer Center at St. Joseph Medical Center
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center - Tacoma
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Health Sciences Center - Charleston
    • Parkersburg, West Virginia, United States, 26102
      • Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic - Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Care at Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and Medical College of Wisconsin
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic - Lakeland Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic - Indianhead Center
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital Regional Cancer Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspiration and biopsy* within the past 14 days

  • No M3 disease NOTE: *Patients with marked leukocytosis may be registered before the availability of biopsy results if the absolute blast count is ≥ 100,000 cells/µL
• No blastic transformation of chronic myelogenous leukemia
• No pre-existing hematologic disorder evolving to AML (e.g., myelodysplasia or secondary leukemia)

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• Zubrod 0-3

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• No known hepatitis B or C infection
• No known liver disease

Renal

• Not specified

Cardiovascular

• LVEF ≥ 50% by MUGA or echocardiogram
• No unstable cardiac arrhythmias
• No unstable angina

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

  • Prior hydroxyurea to control high cell counts allowed
• No more than 1 prior dose of intrathecal chemotherapy for acute leukemia
• Concurrent intrathecal chemotherapy allowed during induction therapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Post-consolidation GO; Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.	Drug: gemtuzumab ozogamicin; Given IV, induction Arm1 6mg/m2 D4; post-consolidation 5mg/m2 3 doses >/= 28 days apart; Other Names: mylotarg
Other: Post-consolidation observation; Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.	Other: observation; No treatment given
Active Comparator: Induction 7+3; Standard induction regimen of 7 days of Ara-C (cytosine arabinoside) and 3 days of daunomycin	Drug: Cytosine arabinoside; IV; induction Arms1/2 and reinduction 100 mg/m2/d days 1-7; consolidation 3gm/m2 q3hrs D1, 3, 5; Other Names: Ara-C; Drug: Daunomycin; IV; induction Arm1 45mg/m2 D1-3; Arm2 and reinduction 60 mg/m2 D1-3; Other Names: daunorubicin
Active Comparator: Induction 7+3+GO; Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C and 3 days of daunomycin	Drug: Cytosine arabinoside; IV; induction Arms1/2 and reinduction 100 mg/m2/d days 1-7; consolidation 3gm/m2 q3hrs D1, 3, 5; Other Names: Ara-C; Drug: Daunomycin; IV; induction Arm1 45mg/m2 D1-3; Arm2 and reinduction 60 mg/m2 D1-3; Other Names: daunorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Disease-free Survival (DFS)	Measured from data of randomization to post-consolidation therapy until relapse from complete response or death from any cause, with observations censored at the date of last contact for patients last known to be alive without report of relapse.	After completing any treatment, every 6 months for 2 years, than annually for years 3-5
Complete Remission		After induction therapy was completed (1 or 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event	For induction, daily for the first 10 days, then twice weekly until consolidation treatment. Weekly during consolidation treatment. Weekly if randomized to post-consolidation G.O.

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Stephen H. Petersdorf, MD, Seattle Cancer Care Alliance

Publications and helpful links

General Publications

• Medeiros BC, Othus M, Fang M, Appelbaum FR, Erba HP. Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia. Haematologica. 2015 Mar;100(3):331-5. doi: 10.3324/haematol.2014.117267. Epub 2014 Dec 19.
• Medeiros BC, Othus M, Estey EH, Fang M, Appelbaum FR. Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia. Br J Haematol. 2014 Jan;164(2):245-50. doi: 10.1111/bjh.12625. Epub 2013 Oct 28.
• Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. doi: 10.1182/blood-2013-01-466706. Epub 2013 Apr 16.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 14, 2004
• First Submitted That Met QC Criteria: June 15, 2004
• First Posted (Estimate): June 16, 2004

Study Record Updates

• Last Update Posted (Estimate): September 30, 2015
• Last Update Submitted That Met QC Criteria: September 25, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); untreated adult acute myeloid leukemia; adult acute erythroid leukemia (M6); 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 myelomonocytic leukemia (M4); adult acute basophilic leukemia; adult acute eosinophilic leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin; Gemtuzumab
• Other Study ID Numbers: S0106 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)