RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Combining more than one drug may kill more cancer cells. It is
not yet known if combination chemotherapy with vinblastine is more effective than
combination chemotherapy with vincristine in treating advanced anaplastic large cell
lymphoma.
PURPOSE: Randomized phase III trial to compare the effectiveness of two combination
chemotherapy regimens with either vinblastine or vincristine in treating patients who have
newly diagnosed advanced anaplastic large cell lymphoma.
- Compare the efficacy of a consolidation chemotherapy regimen comprising doxorubicin and
prednisone in combination with vincristine vs vinblastine, in terms of event-free
survival, in patients with advanced anaplastic large cell lymphoma.
- Correlate biological tumor characteristics and outcome in patients treated with these
regimens.
OUTLINE: This is a randomized, multicenter study.
Patients are randomized at enrollment to receive either Standard APO regimen or a
consolidation regimen including vinblastine (VBL).
- Induction therapy: All Patients receive doxorubicin IV over 15 minutes on days 1 and
22; vincristine IV on days 1, 8, 15, 22, and 29; oral prednisone 3 times daily on days
1-28; and intrathecal (IT) methotrexate on days 1, 8, and 22 (patients with central
nervous system (CNS) disease at diagnosis receive additional methotrexate IT on days
15, 29, and 36).
Patients undergo restaging after Induction such that consolidation therapy is started on day
43. All patients with complete response (CR), complete response unconfirmed (CRu) or partial
response (PR) proceed to Consolidation based on CT or MRI scans at the end of induction
(week 6). All other patients will be removed from protocol therapy and will be followed
until they meet the criteria for off study. Follow-up data will be required unless consent
is withdrawn.
- Standard APO (Arm I): Patients receive course-specific regimens without vinblastine.
- Courses 1-3: Patients receive doxorubicin IV over 15 minutes, vincristine IV, and
methotrexate IT on day 1 and oral prednisone three times daily and oral
mercaptopurine once daily on days 1-5.
- Courses 6-15: Patients receive vincristine, prednisone, and mercaptopurine as in
- Consolidation with vinblastine (Arm II): Patients receive course-specific regimens
- Courses 1-3: Patients receive doxorubicin, methotrexate IT, prednisone, and
mercaptopurine as in arm I and vinblastine IV over 1 minute on days 1, 8, and 15.
- Courses 4-5: Patients receive doxorubicin, prednisone, and mercaptopurine as in
vinblastine as in arm II (courses 1-3), and methotrexate IV on day 1.
In both arms and all courses, treatment repeats every 21 days for up to 15 courses in the
absence of disease progression or unacceptable toxicity.
Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1
year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 200-250 patients (100-125 per treatment arm) will be accrued
for this study within 5 years.
Minimum age: N/A.
Maximum age: 20 Years.
Gender(s): Both.
Centre Hospitalier Universitaire de Quebec, Quebec G1V 4G2, Canada
San Jorge Children's Hospital, Santurce 00912, Puerto Rico
Swiss Pediatric Oncology Group Bern, Bern 3010, Switzerland
Swiss Pediatric Oncology Group Geneva, Geneva 1205, Switzerland
Swiss Pediatric Oncology Group Lausanne, Lausanne 1011, Switzerland
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States
Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada
University of Alberta Hospital, Edmonton, Alberta T6G 1Z2, Canada
Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada
Southern California Permanente Medical Group, Downey, California 90027, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States
Children's Hospital Central California, Madera, California 93638-8762, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States
Sutter Cancer Center, Sacramento, California 95816, United States
Rady Children's Hospital - San Diego, San Diego, California 92123-4282, United States
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States
Stanford Cancer Center, Stanford, California 94305-5824, United States
Children's Hospital Center for Cancer and Blood Disorders, Aurora, Colorado 80045, United States
Presbyterian - St. Luke's Medical Center, Denver, Colorado 80218, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States
Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
Broward General Medical Center Cancer Center, Fort Lauderdale, Florida 33316, United States
Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States
Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States
Nemours Children's Clinic, Jacksonville, Florida 32207, United States
Baptist-South Miami Regional Cancer Program, Miami, Florida 33176, United States
Miami Children's Hospital, Miami, Florida 33155, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando, Orlando, Florida 32803-1273, United States
M.D. Anderson Cancer Center at Orlando, Orlando, Florida 32806, United States
Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States
All Children's Hospital, St. Petersburg, Florida 33701, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States
Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States
Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States
MBCCOP - Medical College of Georgia Cancer Center, Augusta, Georgia 30912-3730, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia 31403-3089, United States
Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center, Boise, Idaho 83712-6297, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States
Advocate Christ Medical Center, Oak Lawn, Illinois 60453, United States
Advocate Lutheran General Cancer Care Center, Park Ridge, Illinois 60068-1174, United States
Saint Jude Midwest Affiliate, Peoria, Illinois 61637, United States
Simmons Cooper Cancer Institute, Springfield, Illinois 62794-9677, United States
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States
St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States
Blank Children's Hospital, Des Moines, Iowa 50309, United States
Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242-1002, United States
Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States
Kosair Children's Hospital, Louisville, Kentucky 40232, United States
Tulane Cancer Center Office of Clinical Research, Alexandria, Louisiana 71315-3198, United States
CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Floating Hospital for Children at Tufts - New England Medical Center, Boston, Massachusetts 02111, United States
Baystate Regional Cancer Program at D'Amour Center for Cancer Care, Springfield, Massachusetts 01199-0001, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center, Ann Arbor, Michigan 48109-0286, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Hurley Medical Center, Flint, Michigan 48503, United States
Butterworth Hospital at Spectrum Health, Grand Rapids, Michigan 49503-2560, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-5381, United States
Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States
Masonic Cancer Center at University of Minnesota, Minneapolis, Minnesota 55455, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States
Children's Hospital, Omaha, Nebraska 68114-4113, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States
CCOP - Nevada Cancer Research Foundation, Las Vegas, Nevada 89109-2306, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States
Overlook Hospital, Morristown, New Jersey 07962, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
St. Joseph's Hospital and Medical Center, Paterson, New Jersey 07503, United States
University of New Mexico Cancer Center, Albuquerque, New Mexico 87131-5636, United States
Westmead Institute for Cancer Research at Westmead Hospital, Westmead, New South Wales 2145, Australia
Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States
Brooklyn Hospital Center, Brooklyn, New York 11201-5493, United States
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States
Schneider Children's Hospital, New Hyde Park, New York 11040, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
New York Medical College, Valhalla, New York 10595, United States
Janeway Children's Health and Rehabilitation Centre, St. John's, Newfoundland and Labrador A1B 3V6, Canada
Mission Hospitals - Memorial Campus, Asheville, North Carolina 28801, United States
Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States
Presbyterian Cancer Center at Presbyterian Hospital, Charlotte, North Carolina 28233-3549, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Leo W. Jenkins Cancer Center at ECU Medical School, Greenville, North Carolina 27835-6028, United States
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States
CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States
IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada
Akron Children's Hospital, Akron, Ohio 44308-1062, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States
Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States
Nationwide Children's Hospital, Columbus, Ohio 43205-2696, United States
Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States
Medical University of Ohio Cancer Center, Toledo, Ohio 43614, United States
Toledo Hospital, Toledo, Ohio 43606, United States
Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States
McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada
Children's Hospital of Western Ontario, London, Ontario N6A 5W9, Canada
Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Legacy Emanuel Hospital and Health Center and Children's Hospital, Portland, Oregon 97227, United States
Oregon Health and Science University Cancer Institute, Portland, Oregon 97239-3098, United States
Lehigh Valley Hospital - Muhlenberg, Bethlehem, Pennsylvania 18017, United States
Geisinger Cancer Institute at Geisinger Health, Danville, Pennsylvania 17822-0001, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada
Royal Children's Hospital, Brisbane, Queensland 4029, Australia
Rhode Island Hospital Comprehensive Cancer Center, Providence, Rhode Island 02903, United States
Allan Blair Cancer Centre at Pasqua Hospital, Regina, Saskatchewan S4T 7T1, Canada
Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada
Greenville Hospital Cancer Center, Greenville, South Carolina 29605, United States
Sanford Cancer Center at Sanford USD Medical Center, Sioux Falls, South Dakota 57117-5039, United States
T.C. Thompson Children's Hospital, Chattanooga, Tennessee 37403, United States
East Tennessee Children's Hospital, Knoxville, Tennessee 37901, United States
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo, Amarillo, Texas 79106, United States
Dell Children's Medical Center of Central Texas, Austin, Texas 78723, United States
Driscoll Children's Hospital, Corpus Christi, Texas 78411, United States
Medical City Dallas Hospital, Dallas, Texas 75230, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States
Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States
M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Covenant Children's Hospital, Lubbock, Texas 79410, United States
Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States
Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States
Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05401, United States
Children's Hospital of The King's Daughters, Norfolk, Virginia 23507-1971, United States
Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Carilion Medical Center for Children at Roanoke Community Hospital, Roanoke, Virginia 24014, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Providence Cancer Center at Sacred Heart Medical Center, Spokane, Washington 99220-2555, United States
Mary Bridge Children's Hospital and Health Center - Tacoma, Tacoma, Washington 98405, United States
West Virginia University Health Sciences Center - Charleston, Charleston, West Virginia 25302, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
St. Vincent Hospital Regional Cancer Center, Green Bay, Wisconsin 54307-3508, United States
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States