Acute Lymphoblastic LeukemiaPhase 3NCT00075725
Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
A Phase 3 study testing Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride in people with Acute Lymphoblastic Leukemia and Adult B Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 234 sites in 5 countries.
Trial summary
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly… Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia, Childhood B Acute Lymphoblastic Leukemia
- What is being tested?
- Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,154 participants
- Where
- 234 sitesin 5 countries
- Study dates
- 29 Dec 2003to 31 Mar 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Must be eligible for and enrolled on classification study COG-AALL03B1
- Newly diagnosed B-precursor acute lymphoblastic leukemia
- WBC > 50,000/mm^3 for patients age 1 to 9
- Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease
- Whit blood cell (WBC) criteria:
- Age 1 - 9 years: WBC >= 50,000/uL
Show all 13Show fewer
- Age 10 - 30 years: any WBC
- Prior steroid therapy: any WBC
- Testicular disease: any WBC
- Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
- Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Who cannot join
- Patients with Down syndrome are ineligible to enroll onto this study
Trial locations and contacts
234 sites in 5 countries.
234 sites in 5 countries
United States208 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Augusta University Medical Center
Augusta, Georgia, 30912
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Tufts Children's Hospital
Boston, Massachusetts, 02111
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Brooklyn Hospital Center
Brooklyn, New York, 11201
Brookdale Hospital Medical Center
Brooklyn, New York, 11212
Maimonides Medical Center
Brooklyn, New York, 11219
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
West Virginia University Charleston Division
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Columbia Regional
Columbia, Missouri, 65201
University of Missouri - Ellis Fischel
Columbia, Missouri, 65212
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Children's Hospital
Dayton, Ohio, 45404
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Ascension Saint John Hospital
Detroit, Michigan, 48236
Kaiser Permanente Downey Medical Center
Downey, California, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Michigan State University Clinical Center
East Lansing, Michigan, 48824-7016
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
University of Connecticut
Farmington, Connecticut, 06030
Hurley Medical Center
Flint, Michigan, 48503
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
Lee Memorial Health System
Fort Myers, Florida, 33901
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
University of Texas Medical Branch
Galveston, Texas, 77555-0565
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
East Carolina University
Greenville, North Carolina, 27834
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Tripler Army Medical Center
Honolulu, Hawaii, 96859
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Loma Linda University Medical Center
Loma Linda, California, 92354
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars Sinai Medical Center
Los Angeles, California, 90048
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Norton Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Banner Children's at Desert
Mesa, Arizona, 85202
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Miami Cancer Institute
Miami, Florida, 33176
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
NYU Winthrop Hospital
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
USA Health Strada Patient Care Center
Mobile, Alabama, 36604
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Mount Sinai Hospital
New York, New York, 10029
NYP/Weill Cornell Medical Center
New York, New York, 10065
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
Orlando Health Cancer Institute
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Sacred Heart Hospital
Pensacola, Florida, 32504
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Naval Medical Center - Portsmouth
Portsmouth, Virginia, 23708-2197
Rhode Island Hospital
Providence, Rhode Island, 02903
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Carilion Children's
Roanoke, Virginia, 24014
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Beaumont Children's Hospital-Royal Oak
Royal Oak, Michigan, 48073
William Beaumont Hospital-Royal Oak
Royal Oak, Michigan, 48073
Sutter Medical Center Sacramento
Sacramento, California, 95816
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Children's Hospital and Clinic-Saint Paul
Saint Paul, Minnesota, 55102
Primary Children's Hospital
Salt Lake City, Utah, 84113
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Santa Barbara Cottage Hospital
Santa Barbara, California, 93102
Memorial Health University Medical Center
Savannah, Georgia, 31404
Maine Children's Cancer Program
Scarborough, Maine, 04074
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Baystate Medical Center
Springfield, Massachusetts, 01199
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Stony Brook University Medical Center
Stony Brook, New York, 11794
Overlook Hospital
Summit, New Jersey, 07902
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Madigan Army Medical Center
Tacoma, Washington, 98431
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Scott and White Memorial Hospital
Temple, Texas, 76508
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Mercy Children's Hospital
Toledo, Ohio, 43608
University of Toledo
Toledo, Ohio, 43614
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
Natalie Warren Bryant Cancer Center at Saint Francis
Tulsa, Oklahoma, 74136
New York Medical College
Valhalla, New York, 10595
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Hospital
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Tod Children's Hospital - Forum Health
Youngstown, Ohio, 44501
Canada15 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Children's Hospital
London, Ontario, N6A 5W9
Victoria Hospital
London, Ontario, N6K 1C2
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
Janeway Child Health Centre
St. John's, Newfoundland and Labrador, A1B 3V6
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia5 sites
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Royal Children's Hospital-Brisbane
Herston, Queensland, 4029
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia, 5006
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
New Zealand3 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
Wellington Children's Hospital
Wellington, 6002
Switzerland3 sites
Swiss Pediatric Oncology Group - Bern
Bern, 3010
Swiss Pediatric Oncology Group - Geneva
Geneva, 1205
Swiss Pediatric Oncology Group - Lausanne
Lausanne, 1011
About this study
Official title: High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
Read the detailed description
OBJECTIVES:
- Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.
II. Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction.
III. Determine the relative safety and efficacy of high-dose methotrexate (5gm/m^2) with leucovorin rescue compared to escalating methotrexate without leucovorin rescue (Capizzi I) during interim maintenance I.
IV. Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS).
- Correlate early marrow response status with day-29 MRD status. VI. Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early response (slow early response [SER] vs rapid early response [RER]). Induction therapy: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenously (IV) and daunorubicin IV on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-14, methotrexate (MTX) IT on days 8 and 29* and pegaspargase intramuscularly (IM) once on day 4, 5, or 6.
NOTE: *Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts on cytospin) also receive MTX IT on days 15 and 22.
ARM II: Patients receive induction therapy as in Arm I.
ARM III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in Arm I. Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29.
ARM IV: Patients receive induction therapy as in Arm III.
Patients in all arms are evaluated at day 29 of induction therapy. Patients with M3 disease are removed from study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI disease and at least 1% MRD receive extended induction therapy for 2 additional weeks. Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031.
Extended induction therapy: Patients continue to receive therapy on the arm to which they were originally randomized.
ARMS I and II: Patients receive dexamethasone PO or IV BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1 and pegaspargase IM on day 4, 5, or 6 and are then reevaluated.
ARMS III and IV: Patients receive prednisone PO or IV BID on days 1-14, and vincristine, daunorubicin, and pegaspargase as in Arms I and II and are then reevaluated.
Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study.
Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine (MP) PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43 and MTX* IT on days 1, 8, 15, and 22. Patients with testicular disease also receive radiotherapy to the testes.
NOTE: *Patients with CNS3 disease receive MTX on days 1 and 8 only.
Interim maintenance therapy I: Patients continue to receive treatment on the arm to which they were originally randomized.
ARM I: (escalating-dose MTX) Patients receive vincristine IV and escalating-dose MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21.
ARM II: (high-dose MTX) Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, MP PO on days 1-56 and IT MTX on days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses, beginning 42 hours after start of each MTX infusion.
ARM III: (escalating-dose MTX) Patients receive interim maintenance I therapy as in Arm I.
ARM IV: (high-dose MTX) Patients receive interim maintenance I therapy as in Arm II.
DELAYED INTENSIFICATION THERAPY I: All patients receive vincristine IV on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over, doxorubicin IV on days 1, 8, and 15, pegaspargase IM on day 4, 5, or 6 AND day 43, cyclophosphamide IV over 30 minutes on day 29, cytarabine IV or SC on days 30-33 and 37-40, thioguanine PO on days 29-42 and MTX IT on days 1, 29, and 36.After delayed intensification I, SER patients proceed to interim maintenance II and delayed intensification II. RER patients proceed directly to maintenance.
INTERIM MAINTENANCE THERAPY II: All patients receive vincristine IV and MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 21. Patients then proceed to delayed intensification II.
DELAYED INTENSIFICATION THERAPY II: All patients receive therapy as in delayed intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days, beginning on day 29. All other SER patients, patients with MLL rearrangements, and some patients pretreated with steroids (> 48 hours within the week prior to diagnosis) receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29. Patients then proceed to maintenance therapy.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57, dexamethasone PO BID on days 1-5, 29-33, and 57-61, MP PO on days 1-84, MTX IT on day 1*; and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
NOTE: *RER (who did not undergo CRT) patients also receive MTX IT on day 29 for maintenance courses 1-4.
In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients. Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
- Conditions
- Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia, Childhood B Acute Lymphoblastic Leukemia
- Being tested
- Cyclophosphamide, Cytarabine, Daunorubicin Hydrochloride, Dexamethasone, Doxorubicin Hydrochloride
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IT, SC, or IV
Daunorubicin HydrochlorideDrug
Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin
Given IV
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT or IV
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase
Given IM
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO or IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radiation therapy
ThioguanineDrug
Also called 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol
Given PO
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | Patients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Radiation: Radiation Therapy; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Arm II | Active comparator | Patients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Radiation: Radiation Therapy; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Arm III | Experimental | Patients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5.
Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisone; Radiation: Radiation Therapy; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Arm IV | Experimental | Patients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5.
Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisone; Radiation: Radiation Therapy; Drug: Thioguanine; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
Event Free Probability.
Measured: 5 years
Secondary outcomes (6)
Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
Measured: 5 Years
Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).
Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells.
Measured: 5 years
Correlation of Early Marrow Response Status With MRD Positive.
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
Measured: Day 29
Correlation of Early Marrow Response Status With MRD Negative.
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells.
Measured: Day 29
Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells.
Measured: 5 years
Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).
Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2004 (estimated)
- Study start29 Dec 2003
- Primary completion31 Dec 2010
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3,154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Eric C Larsen, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00075725
- Sponsor's protocol ID
- AALL0232
- Other IDs
- NCI-2009-00301, COG-AALL0232, CDR0000349182, 11723, AALL0232, AALL0232, U10CA098543
- Status last verified
- Apr 2021
- First submitted
- 9 Jan 2004
- Last updated
- 27 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Orgel E, Maese LD, Devidas M, Militano O, Rau RE, Angiolillo AL, McNeer JL, Schore RJ, Borowitz MJ, Wood B, Raetz EA, Silverman LB, Winick NJ, Larsen EC, Carroll WL, Winter SS, Dunsmore KP, Hunger SP, Loh ML. Toxicity from asparaginase during acute lymphoblastic leukemia induction: a report from the Children's Oncology Group. Blood Adv. 2026 Jul 28;10(14):4923-4930. doi: 10.1182/bloodadvances.2026019870.
PubMed 42085640Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Oct 10;42(29):3491-3503. doi: 10.1200/JCO.23.02238. Epub 2024 Aug 9.
PubMed 39121442Escherich CS, Chen W, Li Y, Yang W, Nishii R, Li Z, Raetz EA, Devidas M, Wu G, Nichols KE, Inaba H, Pui CH, Jeha S, Camitta BM, Larsen E, Hunger SP, Loh ML, Yang JJ. Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children. Blood. 2024 May 30;143(22):2270-2283. doi: 10.1182/blood.2023023336.
PubMed 38446568Rabin KR, Devidas M, Chen Z, Ji L, Kairalla J, Hitzler JK, Yang JJ, Carroll AJ, Heerema NA, Borowitz MJ, Wood BL, Roberts KG, Mullighan CG, Harvey RC, Chen IM, Willman CL, Reshmi SC, Gastier-Foster JM, Bhojwani D, Rheingold SR, Maloney KW, Mattano LA, Larsen EC, Schore RJ, Burke MJ, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Angiolillo AL. Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. J Clin Oncol. 2024 Jan 10;42(2):218-227. doi: 10.1200/JCO.23.00389. Epub 2023 Oct 27.
PubMed 37890117Advani AS, Larsen E, Laumann K, Luger SM, Liedtke M, Devidas M, Chen Z, Yin J, Foster MC, Claxton D, Coffan K, Tallman MS, Appelbaum FR, Erba H, Stone RM, Hunger SP, McNeer JL, Loh ML, Raetz E, Winick N, Carroll W, Larson RA, Stock W. Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia. Blood Adv. 2021 Jan 26;5(2):504-512. doi: 10.1182/bloodadvances.2020002439.
PubMed 33496745Wood B, Wu D, Crossley B, Dai Y, Williamson D, Gawad C, Borowitz MJ, Devidas M, Maloney KW, Larsen E, Winick N, Raetz E, Carroll WL, Hunger SP, Loh ML, Robins H, Kirsch I. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. Blood. 2018 Mar 22;131(12):1350-1359. doi: 10.1182/blood-2017-09-806521. Epub 2017 Dec 28.
PubMed 29284596Karol SE, Mattano LA Jr, Yang W, Maloney KW, Smith C, Liu C, Ramsey LB, Fernandez CA, Chang TY, Neale G, Cheng C, Mardis E, Fulton R, Scheet P, San Lucas FA, Larsen EC, Loh ML, Raetz EA, Hunger SP, Devidas M, Relling MV. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood. 2016 Feb 4;127(5):558-64. doi: 10.1182/blood-2015-10-673848. Epub 2015 Nov 20.
PubMed 26590194Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr, Relling MV. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood. 2015 Oct 8;126(15):1770-6. doi: 10.1182/blood-2015-05-643601. Epub 2015 Aug 11.
PubMed 26265699Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, Nachman JB, Carroll AJ, Heerema NA, Gastier-Foster JM, Willman CL, Dai Y, Winick NJ, Hunger SP, Carroll WL, Larsen E. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015 Aug 20;126(8):964-71. doi: 10.1182/blood-2015-03-633685. Epub 2015 Jun 29.
PubMed 26124497Fernandez CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.
PubMed 24970932
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT00075725
- Acronym / sponsor ID
- AALL0232
- Conditions
- Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia, Childhood B Acute Lymphoblastic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,154 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 29 Dec 2003 (actual)
- Primary completion
- 31 Dec 2010 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 13 Jan 2004 (estimated)
- Results
- Posted 6 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia (ALL). Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium, work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
Detailed description
OBJECTIVES:
- Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens.
II. Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction.
III. Determine the relative safety and efficacy of high-dose methotrexate (5gm/m^2) with leucovorin rescue compared to escalating methotrexate without leucovorin rescue (Capizzi I) during interim maintenance I.
IV. Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS).
- Correlate early marrow response status with day-29 MRD status. VI. Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early response (slow early response [SER] vs rapid early response [RER]). Induction therapy: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenously (IV) and daunorubicin IV on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-14, methotrexate (MTX) IT on days 8 and 29* and pegaspargase intramuscularly (IM) once on day 4, 5, or 6.
NOTE: *Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts on cytospin) also receive MTX IT on days 15 and 22.
ARM II: Patients receive induction therapy as in Arm I.
ARM III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in Arm I. Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29.
ARM IV: Patients receive induction therapy as in Arm III.
Patients in all arms are evaluated at day 29 of induction therapy. Patients with M3 disease are removed from study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI disease and at least 1% MRD receive extended induction therapy for 2 additional weeks. Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031.
Extended induction therapy: Patients continue to receive therapy on the arm to which they were originally randomized.
ARMS I and II: Patients receive dexamethasone PO or IV BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1 and pegaspargase IM on day 4, 5, or 6 and are then reevaluated.
ARMS III and IV: Patients receive prednisone PO or IV BID on days 1-14, and vincristine, daunorubicin, and pegaspargase as in Arms I and II and are then reevaluated.
Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study.
Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine (MP) PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43 and MTX* IT on days 1, 8, 15, and 22. Patients with testicular disease also receive radiotherapy to the testes.
NOTE: *Patients with CNS3 disease receive MTX on days 1 and 8 only.
Interim maintenance therapy I: Patients continue to receive treatment on the arm to which they were originally randomized.
ARM I: (escalating-dose MTX) Patients receive vincristine IV and escalating-dose MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21.
ARM II: (high-dose MTX) Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, MP PO on days 1-56 and IT MTX on days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses, beginning 42 hours after start of each MTX infusion.
ARM III: (escalating-dose MTX) Patients receive interim maintenance I therapy as in Arm I.
ARM IV: (high-dose MTX) Patients receive interim maintenance I therapy as in Arm II.
DELAYED INTENSIFICATION THERAPY I: All patients receive vincristine IV on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over, doxorubicin IV on days 1, 8, and 15, pegaspargase IM on day 4, 5, or 6 AND day 43, cyclophosphamide IV over 30 minutes on day 29, cytarabine IV or SC on days 30-33 and 37-40, thioguanine PO on days 29-42 and MTX IT on days 1, 29, and 36.After delayed intensification I, SER patients proceed to interim maintenance II and delayed intensification II. RER patients proceed directly to maintenance.
INTERIM MAINTENANCE THERAPY II: All patients receive vincristine IV and MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 21. Patients then proceed to delayed intensification II.
DELAYED INTENSIFICATION THERAPY II: All patients receive therapy as in delayed intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days, beginning on day 29. All other SER patients, patients with MLL rearrangements, and some patients pretreated with steroids (> 48 hours within the week prior to diagnosis) receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29. Patients then proceed to maintenance therapy.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57, dexamethasone PO BID on days 1-5, 29-33, and 57-61, MP PO on days 1-84, MTX IT on day 1*; and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
NOTE: *RER (who did not undergo CRT) patients also receive MTX IT on day 29 for maintenance courses 1-4.
In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients. Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I | Active comparator | Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine SulfatePatients in arm I receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. |
| Arm II | Active comparator | Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine SulfatePatients in arm II will receive intrathecal cytarabine in week 1; infusions of vincristine and daunorubicin once a week in weeks 1-4; dexamethasone by mouth or infusion twice a day in weeks 1 and 2; intrathecal methotrexate in weeks 2 and 5 or 2-5; and an injection of pegaspargase in week 1. |
| Arm III | Experimental | Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisone, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine SulfatePatients in arm III will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
| Arm IV | Experimental | Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisone, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine SulfatePatients in arm IV will receive cytarabine, vincristine, daunorubicin, and pegaspargase as in groups one and two. They will also receive prednisone by mouth or infusion twice a day in weeks 1-4 and intrathecal methotrexate in weeks 2 and 5. Some patients in all groups may receive induction therapy for 2 additional weeks. Beginning in week 6 or 7, patients may receive combination chemotherapy by infusion, injection, intrathecally, and by mouth for up to 8 weeks. |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Must be eligible for and enrolled on classification study COG-AALL03B1
- Newly diagnosed B-precursor acute lymphoblastic leukemia
- Whit blood cell (WBC) criteria:
- Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine
- Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented
Key exclusion criteria (1 listed)
- Patients with Down syndrome are ineligible to enroll onto this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IT, SC, or IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| Daunorubicin HydrochlorideAlso: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, DaunoblastinGiven IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO or IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| Doxorubicin HydrochlorideAlso: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, AdriamycinGiven IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven IV | Drug | Arm II, Arm IV |
| MercaptopurineAlso: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 ThiopurineGiven PO | Drug | Arm I, Arm II, Arm III, Arm IV |
| MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IT or IV | Drug | Arm I, Arm II, Arm III, Arm IV |
| PegaspargaseAlso: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-AsparaginaseGiven IM | Drug | Arm I, Arm II, Arm III, Arm IV |
| PrednisoneAlso: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, CortancylGiven PO or IV | Drug | Arm III, Arm IV |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo radiation therapy | Radiation | Arm I, Arm II, Arm III, Arm IV |
| ThioguanineAlso: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiolGiven PO | Drug | Arm I, Arm II, Arm III, Arm IV |
| Vincristine SulfateAlso: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, OncovinGiven IV | Drug | Arm I, Arm II, Arm III, Arm IV |
Primary outcome
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
Time frame: 5 years
Event Free Probability.
6 secondary outcomes
Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)
Time frame: 5 Years
Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).
Time frame: 5 years
Correlation of Early Marrow Response Status With MRD Positive.
Time frame: Day 29
Correlation of Early Marrow Response Status With MRD Negative.
Time frame: Day 29
Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)
Time frame: 5 years
Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42085640Orgel E, Maese LD, Devidas M, Militano O, Rau RE, Angiolillo AL, McNeer JL, Schore RJ, Borowitz MJ, Wood B, Raetz EA, Silverman LB, Winick NJ, Larsen EC, Carroll WL, Winter SS, Dunsmore KP, Hunger SP, Loh ML. Toxicity from asparaginase during acute lymphoblastic leukemia induction: a report from the Children's Oncology Group. Blood Adv. 2026 Jul 28;10(14):4923-4930. doi: 10.1182/bloodadvances.2026019870.
- Derived from this study: PubMed 39121442Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Oct 10;42(29):3491-3503. doi: 10.1200/JCO.23.02238. Epub 2024 Aug 9.
- Derived from this study: PubMed 38446568Escherich CS, Chen W, Li Y, Yang W, Nishii R, Li Z, Raetz EA, Devidas M, Wu G, Nichols KE, Inaba H, Pui CH, Jeha S, Camitta BM, Larsen E, Hunger SP, Loh ML, Yang JJ. Germ line genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children. Blood. 2024 May 30;143(22):2270-2283. doi: 10.1182/blood.2023023336.
- Derived from this study: PubMed 37890117Rabin KR, Devidas M, Chen Z, Ji L, Kairalla J, Hitzler JK, Yang JJ, Carroll AJ, Heerema NA, Borowitz MJ, Wood BL, Roberts KG, Mullighan CG, Harvey RC, Chen IM, Willman CL, Reshmi SC, Gastier-Foster JM, Bhojwani D, Rheingold SR, Maloney KW, Mattano LA, Larsen EC, Schore RJ, Burke MJ, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Angiolillo AL. Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. J Clin Oncol. 2024 Jan 10;42(2):218-227. doi: 10.1200/JCO.23.00389. Epub 2023 Oct 27.
- Derived from this study: PubMed 33496745Advani AS, Larsen E, Laumann K, Luger SM, Liedtke M, Devidas M, Chen Z, Yin J, Foster MC, Claxton D, Coffan K, Tallman MS, Appelbaum FR, Erba H, Stone RM, Hunger SP, McNeer JL, Loh ML, Raetz E, Winick N, Carroll W, Larson RA, Stock W. Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia. Blood Adv. 2021 Jan 26;5(2):504-512. doi: 10.1182/bloodadvances.2020002439.
- Derived from this study: PubMed 29284596Wood B, Wu D, Crossley B, Dai Y, Williamson D, Gawad C, Borowitz MJ, Devidas M, Maloney KW, Larsen E, Winick N, Raetz E, Carroll WL, Hunger SP, Loh ML, Robins H, Kirsch I. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. Blood. 2018 Mar 22;131(12):1350-1359. doi: 10.1182/blood-2017-09-806521. Epub 2017 Dec 28.
- Derived from this study: PubMed 26590194Karol SE, Mattano LA Jr, Yang W, Maloney KW, Smith C, Liu C, Ramsey LB, Fernandez CA, Chang TY, Neale G, Cheng C, Mardis E, Fulton R, Scheet P, San Lucas FA, Larsen EC, Loh ML, Raetz EA, Hunger SP, Devidas M, Relling MV. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood. 2016 Feb 4;127(5):558-64. doi: 10.1182/blood-2015-10-673848. Epub 2015 Nov 20.
- Derived from this study: PubMed 26265699Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr, Relling MV. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood. 2015 Oct 8;126(15):1770-6. doi: 10.1182/blood-2015-05-643601. Epub 2015 Aug 11.
- Derived from this study: PubMed 26124497Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, Nachman JB, Carroll AJ, Heerema NA, Gastier-Foster JM, Willman CL, Dai Y, Winick NJ, Hunger SP, Carroll WL, Larsen E. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015 Aug 20;126(8):964-71. doi: 10.1182/blood-2015-03-633685. Epub 2015 Jun 29.
- Derived from this study: PubMed 24970932Fernandez CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric C Larsen principal investigator
Children's Oncology Group
234 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide, Cytarabine and Daunorubicin Hydrochloride in people with Acute Lymphoblastic Leukemia and Adult B Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 234 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 234 sites in United States, Canada, Australia, New Zealand, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00075725, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2021.