Acute Lymphoblastic LeukemiaPhase 3NCT00103285
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
A Phase 3 study testing 3-Dimensional Conformal Radiation Therapy, Cyclophosphamide and Cytarabine in people with Acute Lymphoblastic Leukemia and Childhood B Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 236 sites in 5 countries.
Trial summary
This randomized phase III trial is studying different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 1 year to 9 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Childhood B Acute Lymphoblastic Leukemia
- What is being tested?
- 3-Dimensional Conformal Radiation Therapy, Cyclophosphamide and Cytarabine
- 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
- 5,377 participants
- Where
- 236 sitesin 5 countries
- Study dates
- 11 Apr 2005to 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 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients must be enrolled on AALL03B1 prior to enrollment on AALL0331
- Initial white blood cells (WBC) < 50,000/ul
- Newly diagnosed B-precursor acute lymphoblastic leukemia
- Standard-risk (SR) disease meeting 1 of the following criteria:
- SR-average by age and WBC
- No unfavorable features
Show all 33Show fewer
- Rapid early responder (RER) by day 15
- CNS 1 or 2
- Minimal residual disease (MRD) negative on day 29
- Trisomies of 4, 10, and 17 or TEL-AML1 translocation and RER and CNS2 allowed
- SR-low by age and WBC
- No unfavorable features
- RER by day 15
- MRD negative on day 29
- CNS1
- Favorable cytogenetics-trisomies of 4, 10, and 17 or TEL-AML translocation
- SR-high
- Unfavorable features meeting ≥ 1 of the following criteria:
- MLL rearrangements and RER
- Steroid pretreatment
- CNS3
- Slow early responder by morphology or MRD
- Patients with Down syndrome are allowed
- Patients with overt testicular disease are not eligible for this study, but may be eligible for AALL0232
- Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment
- Patients receiving prior steroid therapy may be eligible for AALL0331 study
- Patients with a contraindication to additional asparaginase therapy, following Induction, are not eligible for the Standard Risk-Low study, and should be removed from protocol therapy at the end of Induction
- Patients who are assigned to the standard risk-average group following Induction and who meet the HRQOL
- Age at diagnosis >= 2 years (note that this is a more restrictive age range than for the therapeutic component of the study)
- At least one parent with reading comprehension of English or Spanish languages for which validated surveys exist
- Diagnosis at one of the institutions participating in this limited institution correlative study
- A parent or legal guardian must sign a written informed consent/parental permission for all patients
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Who cannot join
None listed.
Trial locations and contacts
236 sites in 5 countries.
236 sites in 5 countries
United States210 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
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
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
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
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
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
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
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-Mount Zion
San Francisco, California, 94115
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
Harbor-University of California at Los Angeles Medical Center
Torrance, California, 90502
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: Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)
This randomized phase III trial is studying different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival (EFS) of children with SR-average acute lymphoblastic leukemia (ALL).
II. Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL.
III. To determine whether the addition of four doses of percutaneous endoscopic gastrostomy (PEG) asparaginase, given once every three weeks during Consolidation and Interim Maintenance phases, will improve the EFS for children with SR-low ALL.
SECONDARY OBJECTIVES:
- Identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.
II. Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur.
III. Correlate day 29 minimal residual disease (MRD) with EFS and overall survival (OS) of patients treated with these regimens.
IV. Correlate early marrow response with day 29 MRD status. V. To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
VI. To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials.
OUTLINE: This is a 2-part, partially randomized, multicenter study. Patients are stratified according to early response to study induction therapy (rapid early response [standard risk (SR)-low or SR-average acute lymphoblastic leukemia (ALL)] vs slow early response [SR-high ALL]). After completion of induction therapy but before proceeding to part II therapy, patients are assigned to 1 of 3 groups based on stratification.
PART I:
INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) < 0.1% OR MRD >= 0.1% and < 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD >= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study.
EXTENDED INDUCTION THERAPY: Patients receive dexamethasone IV or PO BID on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM on day 4, 5, or 6; and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1. Patients with M1 bone marrow and MRD < 1% after extended induction therapy proceed to therapy in part II. Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study.
PART II:
GROUP 1 (SR-low ALL): Patients are randomized to 1 of 2 treatment arms.
ARM I:
STANDARD CONSOLIDATION THERAPY: Patients receive vincristine IV on day 1; mercaptopurine PO on days 1-28; and methotrexate IT on days 1, 8, and 15. Patients with Down syndrome (DS) receive leucovorin calcium (PO) at 48 and 60 hours after each dose of methotrexate IT.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive vincristine IV on days 1 and 29; dexamethasone IV or PO BID on days 1-5 and 29-33; mercaptopurine PO on days 1-50; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, and 50; and methotrexate IT on day 29. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
STANDARD DELAYED INTENSIFICATION (DI) THERAPY: Patients receive vincristine IV on days 1, 8, and 15; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1 and 29. Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM II:
EXPERIMENTAL CONSOLIDATION THERAPY: Patients receive vincristine, mercaptopurine, methotrexate, and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22.
EXPERIMENTAL INTERIM MAINTENANCE THERAPY: Patients receive vincristine, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36.Standard DI therapy: Patients receive standard DI therapy as in arm I.
GROUP 2 (SR-average ALL): Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I.
ARM II:
STANDARD CONSOLIDATION THERAPY: Patients receive standard consolidation therapy as in group 1, arm I. Augmented interim maintenance therapy: Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Augmented DI therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours 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 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1, 29, and 36. Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM III:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine 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 methotrexate IT on days 1, 8, 15*, and 22*. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT*.
NOTE: *Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive standard interim maintenance therapy as in group 1, arm I.
STANDARD DI THERAPY: Patients receive standard DI therapy as in group 1, arm I.
ARM IV:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II.
AUGMENTED DI THERAPY: Patients receive augmented DI therapy as in group 2, arm II.
GROUP 3 (SR-high ALL): Patients receive the following therapy: Intensified consolidation therapy: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE* THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses.
NOTE: *As of Amendment #7, all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with high-dose methotrexate (IM HD) rather than Capizzi methotrexate. Patients should then proceed to ADI 2 and then Maintenance.
AUGMENTED DI* THERAPY: Patients receive augmented DI therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses**.
NOTE: *As of Amendment #7, all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with IM HD. Patients should then proceed to ADI 2 and then Maintenance.
NOTE: **Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only; these patients do not receive methotrexate on day 36, thioguanine, or leucovorin calcium.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and methotrexate IT* on day 1. Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients.
NOTE: *SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males.
After the completion of study treatment, patients are followed every 1-2 months for 2 years, every 3 months for 1 year, and then every 6-12 months for 2 years.
- Being tested
- 3-Dimensional Conformal Radiation Therapy, Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin Hydrochloride
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-Dimensional Conformal Radiation TherapyRadiation
Also called 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT
Some patients undergo cranial radiotherapy
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 IV or SC
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given IV or PO
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 or IT
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given PO
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IM or IT
PegaspargaseDrug
Also called L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase
Given IM
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 |
|---|---|---|
| Group 0 Induction Therapy | Experimental | All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) < 0.1% OR MRD >= 0.1% and < 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD >= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. Receives: Drug: Cytarabine; Drug: Dexamethasone; Drug: Leucovorin Calcium; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine Sulfate |
| Group 1-SR-low ALL, Arm I (combination chemotherapy) | Active comparator | Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Group 1-SR-low ALL, arm II (combination chemotherapy) | Experimental | Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Dexamethasone; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine Sulfate |
| Group 2-SR-avg ALL, arm I (combination chemotherapy) | Active comparator | Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine |
| Group 2-SR-avg ALL, arm II (combination chemotherapy) | Experimental | Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Group 2-SR-avg ALL, arm III (combination chemotherapy) | Active comparator | Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Group 2-SR-avg ALL, arm IV (combination chemotherapy) | Active comparator | Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine Sulfate |
| Group 3-SR-high ALL, combination chemotherapy | Experimental | Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. Receives: Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival (EFS) for SR-Average ALL Patients
EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Measured: 6 years
Event-free Survival (EFS) for SR-Low Patients
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Measured: 6 years
Secondary outcomes (7)
Health-related Quality of Life Relative to Physical, Social and Emotional Impairment
To identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.Standardized scores will be computed for child function using the gender and age-adjusted scores available from normative data from a healthy population of about 10,000 children. The various domains of family functioning will be assessed using well-validated instruments and analyzed as a dichotomous variable (impaired vs. non-impaired family functioning). Multiple regression analysis will be used to test the effect of family functioning (adjusted for therapy given, age at diagnosis, gender, socioeconomic status and other factors) on child function.
Measured: At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
Event-Free Survival Probability According to MRD Status End Induction (Day 29)
Event-Free survival by Day 29 MRD status (negative vs positive), Event Free Probability (time from study entry to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Measured: MRD at Day 29 of therapy
Overall Survival Probability (OS) According to Induction Day 29 MRD Status
Overall survival by Day 29 MRD status (negative vs positive), Overall survival defined as time from study entry to death or date of last contact for patients who are alive.
Measured: Overall Survival Probability of 6 years
Early Marrow Status (EMS) by MRD Status End Induction (Day 29)
Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative)
Measured: Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
Optimal Time Point for Advance Health Related Quality of Life Intervention
Percentage of patients with elevated Anxiety.
Measured: At 1 month after diagnosis and 3 months post-therapy.
Event-free Survival (EFS) for SR-High Patients.
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Measured: 6 years
Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)
Event-free probability where EFS is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2005 (estimated)
- Study start11 Apr 2005
- Primary completion30 Dec 2013
- 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 (7)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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5,377 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kelly W Maloney, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00103285
- Sponsor's protocol ID
- AALL0331
- Other IDs
- NCI-2009-00302, 05-340, COG-AALL0331, CDR0000409589, AALL0331, AALL0331, U10CA098543
- Status last verified
- Apr 2021
- First submitted
- 7 Feb 2005
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Chen W, Chang TC, Rabin KR, Raetz EA, Devidas M, Hunger SP, Ramirez NC, Mullighan CG, Loh ML, Wu G. Performance of Two-Phase Designs for the Time-to-Event Outcome and a Case Study Assessing the Relapse Risk Associated With B-ALL Subtypes. JCO Clin Cancer Inform. 2025 May;9:e2400223. doi: 10.1200/CCI-24-00223. Epub 2025 May 2.
PubMed 40315406Chang 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 37890117Wood 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 26590194Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013 Jun 27;121(26):5154-7. doi: 10.1182/blood-2013-02-485623. Epub 2013 May 15.
PubMed 23678006
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT00103285
- Acronym / sponsor ID
- AALL0331
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,377 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Apr 2005 (actual)
- Primary completion
- 30 Dec 2013 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 8 Feb 2005 (estimated)
- Results
- Posted 11 Jul 2018
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 different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival (EFS) of children with SR-average acute lymphoblastic leukemia (ALL).
II. Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL.
III. To determine whether the addition of four doses of percutaneous endoscopic gastrostomy (PEG) asparaginase, given once every three weeks during Consolidation and Interim Maintenance phases, will improve the EFS for children with SR-low ALL.
SECONDARY OBJECTIVES:
- Identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.
II. Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur.
III. Correlate day 29 minimal residual disease (MRD) with EFS and overall survival (OS) of patients treated with these regimens.
IV. Correlate early marrow response with day 29 MRD status. V. To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM).
VI. To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials.
OUTLINE: This is a 2-part, partially randomized, multicenter study. Patients are stratified according to early response to study induction therapy (rapid early response [standard risk (SR)-low or SR-average acute lymphoblastic leukemia (ALL)] vs slow early response [SR-high ALL]). After completion of induction therapy but before proceeding to part II therapy, patients are assigned to 1 of 3 groups based on stratification.
PART I:
INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) < 0.1% OR MRD >= 0.1% and < 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD >= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study.
EXTENDED INDUCTION THERAPY: Patients receive dexamethasone IV or PO BID on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM on day 4, 5, or 6; and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1. Patients with M1 bone marrow and MRD < 1% after extended induction therapy proceed to therapy in part II. Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study.
PART II:
GROUP 1 (SR-low ALL): Patients are randomized to 1 of 2 treatment arms.
ARM I:
STANDARD CONSOLIDATION THERAPY: Patients receive vincristine IV on day 1; mercaptopurine PO on days 1-28; and methotrexate IT on days 1, 8, and 15. Patients with Down syndrome (DS) receive leucovorin calcium (PO) at 48 and 60 hours after each dose of methotrexate IT.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive vincristine IV on days 1 and 29; dexamethasone IV or PO BID on days 1-5 and 29-33; mercaptopurine PO on days 1-50; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, and 50; and methotrexate IT on day 29. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
STANDARD DELAYED INTENSIFICATION (DI) THERAPY: Patients receive vincristine IV on days 1, 8, and 15; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1, 8, and 15; pegaspargase IM on day 4, 5, or 6; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1 and 29. Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM II:
EXPERIMENTAL CONSOLIDATION THERAPY: Patients receive vincristine, mercaptopurine, methotrexate, and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22.
EXPERIMENTAL INTERIM MAINTENANCE THERAPY: Patients receive vincristine, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36.Standard DI therapy: Patients receive standard DI therapy as in arm I.
GROUP 2 (SR-average ALL): Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I.
ARM II:
STANDARD CONSOLIDATION THERAPY: Patients receive standard consolidation therapy as in group 1, arm I. Augmented interim maintenance therapy: Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase IM on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Augmented DI therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21; doxorubicin hydrochloride IV over 15 minutes to 2 hours 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 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1, 29, and 36. Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT.
ARM III:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine 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 methotrexate IT on days 1, 8, 15*, and 22*. Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT*.
NOTE: *Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium.
STANDARD INTERIM MAINTENANCE THERAPY: Patients receive standard interim maintenance therapy as in group 1, arm I.
STANDARD DI THERAPY: Patients receive standard DI therapy as in group 1, arm I.
ARM IV:
INTENSIFIED CONSOLIDATION THERAPY: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II.
AUGMENTED DI THERAPY: Patients receive augmented DI therapy as in group 2, arm II.
GROUP 3 (SR-high ALL): Patients receive the following therapy: Intensified consolidation therapy: Patients receive intensified consolidation therapy as in group 2, arm III.
AUGMENTED INTERIM MAINTENANCE* THERAPY: Patients receive augmented interim maintenance therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses.
NOTE: *As of Amendment #7, all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with high-dose methotrexate (IM HD) rather than Capizzi methotrexate. Patients should then proceed to ADI 2 and then Maintenance.
AUGMENTED DI* THERAPY: Patients receive augmented DI therapy as in group 2, arm II. Treatment repeats every 56 days for 2 courses**.
NOTE: *As of Amendment #7, all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned. Upon completion of ADI 1, patients should receive a second Interim Maintenance phase with IM HD. Patients should then proceed to ADI 2 and then Maintenance.
NOTE: **Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only; these patients do not receive methotrexate on day 36, thioguanine, or leucovorin calcium.
MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and methotrexate IT* on day 1. Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients.
NOTE: *SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males.
After the completion of study treatment, patients are followed every 1-2 months for 2 years, every 3 months for 1 year, and then every 6-12 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Group 0 Induction Therapy | Experimental | Drug: Cytarabine, Drug: Dexamethasone, Drug: Leucovorin Calcium, Drug: Methotrexate, Drug: Pegaspargase, Drug: Vincristine SulfateAll patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) < 0.1% OR MRD >= 0.1% and < 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD >= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study. |
| Group 1-SR-low ALL, Arm I (combination chemotherapy) | Active comparator | Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine SulfatePatients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years |
| Group 1-SR-low ALL, arm II (combination chemotherapy) | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Dexamethasone, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Vincristine SulfatePatients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
| Group 2-SR-avg ALL, arm I (combination chemotherapy) | Active comparator | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: ThioguaninePatients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
| Group 2-SR-avg ALL, arm II (combination chemotherapy) | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Methotrexate, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine SulfatePatients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
| Group 2-SR-avg ALL, arm III (combination chemotherapy) | Active comparator | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine SulfatePatients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
| Group 2-SR-avg ALL, arm IV (combination chemotherapy) | Active comparator | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine SulfatePatients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
| Group 3-SR-high ALL, combination chemotherapy | Experimental | Radiation: 3-Dimensional Conformal Radiation Therapy, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Thioguanine, Drug: Vincristine SulfatePatients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years. |
Who may qualify
- Ages
- 1 year to 9 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (33 listed)
- Patients must be enrolled on AALL03B1 prior to enrollment on AALL0331
- Initial white blood cells (WBC) < 50,000/ul
- Newly diagnosed B-precursor acute lymphoblastic leukemia
- Patients with Down syndrome are allowed
- Patients with overt testicular disease are not eligible for this study, but may be eligible for AALL0232
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| 3-Dimensional Conformal Radiation TherapyAlso: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRTSome patients undergo cranial radiotherapy | Radiation | Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| 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 IV or SC | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven IV or PO | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| 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 or IT | Drug | Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven PO | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| MercaptopurineAlso: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 ThiopurineGiven PO | Drug | Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| MethotrexateAlso: Abitrexate, Alpha-Methopterin, Amethopterin, BrimexateGiven IM or IT | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| PegaspargaseAlso: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-AsparaginaseGiven IM | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| ThioguanineAlso: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiolGiven PO | Drug | Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 2-SR-avg ALL, arm I (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
| Vincristine SulfateAlso: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, OncovinGiven IV | Drug | Group 0 Induction Therapy, Group 1-SR-low ALL, Arm I (combination chemotherapy), Group 1-SR-low ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm II (combination chemotherapy), Group 2-SR-avg ALL, arm III (combination chemotherapy), Group 2-SR-avg ALL, arm IV (combination chemotherapy), Group 3-SR-high ALL, combination chemotherapy |
Primary outcome
Event-free Survival (EFS) for SR-Average ALL Patients
Time frame: 6 years
EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Event-free Survival (EFS) for SR-Low Patients
Time frame: 6 years
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
7 secondary outcomes
Health-related Quality of Life Relative to Physical, Social and Emotional Impairment
Time frame: At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
Event-Free Survival Probability According to MRD Status End Induction (Day 29)
Time frame: MRD at Day 29 of therapy
Overall Survival Probability (OS) According to Induction Day 29 MRD Status
Time frame: Overall Survival Probability of 6 years
Early Marrow Status (EMS) by MRD Status End Induction (Day 29)
Time frame: Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
Optimal Time Point for Advance Health Related Quality of Life Intervention
Time frame: At 1 month after diagnosis and 3 months post-therapy.
Event-free Survival (EFS) for SR-High Patients.
Time frame: 6 years
Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)
Time frame: 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40315406Chen W, Chang TC, Rabin KR, Raetz EA, Devidas M, Hunger SP, Ramirez NC, Mullighan CG, Loh ML, Wu G. Performance of Two-Phase Designs for the Time-to-Event Outcome and a Case Study Assessing the Relapse Risk Associated With B-ALL Subtypes. JCO Clin Cancer Inform. 2025 May;9:e2400223. doi: 10.1200/CCI-24-00223. Epub 2025 May 2.
- 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 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 23678006Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013 Jun 27;121(26):5154-7. doi: 10.1182/blood-2013-02-485623. Epub 2013 May 15.
- Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data ArchiveLink provided by the sponsor.
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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.
Kelly W Maloney principal investigator
Children's Oncology Group
236 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 3-Dimensional Conformal Radiation Therapy, Cyclophosphamide and Cytarabine in people with Acute Lymphoblastic Leukemia and Childhood B Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 236 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 33 inclusion and 0 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 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 236 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 11 Jul 2018). 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?
Event-free Survival (EFS) for SR-Average ALL Patients (time frame: 6 years). The study lists 2 primary outcomes in all. 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 NCT00103285, which also lists 7 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 14 Jun 2021.