Comparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia

Leukemia Clinical Trial

Official title:

Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue Versus Oral Methotrexate and Single Versus Double Delayed Intensification for Children With Standard Risk Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005945
• Other study ID #: 1991
• Secondary ID: CCG-1991CDR00000
• Status: Completed
• Phase: Phase 3
• First received: July 5, 2000
• Last updated: February 19, 2016
• Start date: June 2000
• Est. completion date: June 2008

Study information

• Verified date: February 2016
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use 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 childhood acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.

Description:

OBJECTIVES:

• Compare the event-free survival and overall survival of children with standard-risk acute lymphoblastic leukemia treated with escalating-dose IV methotrexate without leucovorin calcium versus oral methotrexate during the interim maintenance phase of therapy.

• Compare the event-free survival and overall survival of these patients after receiving treatment in two delayed intensification phases versus one delayed intensification phase.

• Compare the toxic effects of oral versus escalating-dose intravenous methotrexate in these patients.

• Determine the prognostic significance of the rate of disappearance of peripheral lymphoblasts and lymphocytes during the first week of treatment in these patients.

• Determine the prognostic significance of trisomies of chromosomes 4, 5, 10, and 17 and early treatment response in patients treated with these regimens.

• Determine the prognostic significance of the TEL-AML1 fusion transcript and early treatment response in patients treated with these regimens.

• Determine the minimal residual disease (MRD) by polymerase chain reaction in bone marrow and cerebrospinal fluid at various stages of therapy in these patients.

• Determine the prognostic significance of MRD during various stages of therapy in these patients.

• Determine whether a second delayed intensification therapy improves the prognosis of patients who have MRD at the end of induction therapy.

OUTLINE: This is a randomized, multicenter study. Patients without CNS disease at diagnosis, achieving a specified early marrow response profile and M1 marrow status of less than 5% blasts in the bone marrow (regardless of the proportion of mature lymphocytes) by day 28 of induction therapy, and remaining event free with favorable bone marrow status and cytogenetics between day 21 and 28 of consolidation therapy are randomized to one of four treatment arms. Patients with CNS disease at diagnosis are assigned to treatment arm II and undergo cranial irradiation. Patients with any of the following unfavorable bone marrow features and/or unfavorable cytogenetic features are assigned to the augmented treatment regimen by day 21 of induction chemotherapy or at the beginning of consolidation chemotherapy:

NOTE: All T-cell precursor patients that are not more than 4 months past completion of the delayed intensification phase of therapy should be switched to the augmented regimen as of 3/8/2004. These patients may be switched to the augmented regimen. The protocol gives specific instructions according to the phase of therapy the patients are actually in.

• Unfavorable marrow status:

• M2: 5-25% blasts in bone marrow at day 28 of induction chemotherapy (or at day 14 of induction chemotherapy if day 7 status is M3) OR

• M3: More than 25% blast cell in bone marrow, regardless of the proportion of mature lymphocytes at day 14 of induction chemotherapy

• Unfavorable cytogenetics: Must have 1 of the following:

• t(9;22)(q34;q11)

• t(4;11)(q21;q23)

• Balanced t(1;19)(q23;p13)

• Hypodiploidy with less than 45 chromosomes

• Other 11q23 translocations involving MLL Patients receive standard induction chemotherapy comprising cytarabine (ARA-C) intrathecally (IT) on day 0 or up to 72 hours before day 0; oral dexamethasone (DM) twice daily on days 0-27; vincristine (VCR) IV on days 0, 7, 14, and 21; and pegaspargase (PEG-ASP) intramuscularly (IM) once between days 3-5. Patients without CNS disease at diagnosis receive methotrexate (MTX) IT on days 7 and 28. Patients with CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28.

Patients who have achieved M1 marrow status by day 28 of induction therapy and have favorable early bone marrow response and cytogenetics proceed to standard consolidation therapy once blood counts have recovered. Patients with M3 bone marrow status at day 28 of induction therapy are taken off the protocol. All other patients are assigned to the augmented treatment regimen.

Beginning on day 28 of induction chemotherapy, patients receive standard consolidation chemotherapy comprising VCR IV on day 0 and oral mercaptopurine (MP) on days 0-27. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation 5 days a week for 2 weeks. Patients with testicular disease receive bilateral testicular radiotherapy 5 days a week for 1 week and then for 3 consecutive days during the next week.

NOTE: As of 3/8/2004, patients with T-cell disease who did not achieve M1 marrow status by day 14 of induction OR who did not receive augmented induction and/or consolidation (regardless of early marrow status) receive cranial irradiation.

• Arm I: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising oral DM twice daily on days 0-4 and 28-32; VCR IV on days 0 and 28; oral MTX on days 0, 7, 14, 21, 28, 35, 42, and 49; oral MP on days 0-49; and MTX IT on day 28.

Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV and doxorubicin (DOX) IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on day 3; cyclophosphamide (CTX) IV over 20-30 minutes on day 28; oral thioguanine (TG) on days 28-41; ARA-C IV or subcutaneously (SC) daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.

Beginning on day 56 of delayed intensification chemotherapy, patients receive interim maintenance II chemotherapy identical to interim maintenance I chemotherapy except patients receive MTX IT on days 0 and 28.

Beginning on day 56 of interim maintenance II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.

• Arm II: Patients receive interim maintenance I chemotherapy, delayed intensification chemotherapy, and interim maintenance II chemotherapy as in arm I. Beginning on day 56 of interim maintenance II chemotherapy, patients then receive a second course of delayed intensification chemotherapy followed by maintenance chemotherapy as in arm I.

• Arm III: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV; escalating doses of MTX IV on days 0, 10, 20, 30, and 40; and MTX IT on day 30. Patients then receive delayed intensification chemotherapy as in arm I. Patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the maximum tolerated dose (MTD) attained in interim maintenance I chemotherapy. Patients then receive maintenance chemotherapy as in arm I.

• Arm IV: Patients receive interim maintenance I chemotherapy as in arm III, delayed intensification chemotherapy as in arm I, interim maintenance II chemotherapy as in arm III, delayed intensification II chemotherapy as in arm II, and maintenance chemotherapy as in arm I.

• Augmented Treatment: Patients receive induction chemotherapy comprising daunorubicin IV continuously for 48 hours beginning no later than day 21; oral DM twice daily on days 14-27; and VCR IV on days 14 and 21. Patients without CNS disease at diagnosis receive MTX IT on days 21 and 35. Patients with CNS disease at diagnosis receive MTX IT on days 21 and 28.

NOTE: Patients with T-cell disease should re-start with augmented consolidation and proceed as per the augmented regimen.

Beginning on day 35 of induction chemotherapy, patients receive consolidation therapy comprising CTX IV over 20-30 minutes on days 0 and 28; oral MP on days 0-13 and 28-41; ARA-C IV or SC daily on days 0-3, 7-10, 28-31, and 35-38; VCR IV on days 14, 21, 42, and 49; and PEG-ASP IM on days 14 and 42. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, and 21. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation as in the randomized treatment section. Patients with testicular leukemia receive radiotherapy as in the randomized treatment section.

Beginning on day 63 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV on days 0, 10, 20, 30, and 40; escalating doses of MTX IV on days 10, 20, 30, and 40; PEG-ASP IM on days 1 and 21; and MTX IT on days 0 and 30.

Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification I chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV on days 0, 7, 14, 42, and 49; DOX IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on days 3 and 42; CTX IV over 20-30 minutes on day 28; oral TG on days 28-41; ARA-C IV or SC daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.

NOTE: Patients with T-cell disease who are in interim maintenance I chemotherapy with escalating IV methotrexate should continue this phase and then proceed as per the augmented regimen. If these patients are receiving conventional interim maintenance chemotherapy with oral methotrexate, they should stop and restart the interim maintenance as per the augmented regimen. These patients receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy.

Beginning on day 56 of delayed intensification I chemotherapy, patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the MTD attained in interim maintenance I chemotherapy.

NOTE: Patients with T-cell disease who are in delayed intensification I chemotherapy proceed with this phase, with the addition of 2 vincristine doses on days 42 and 49 and PEG-ASP on day 42. These patients then proceed as per the augmented regimen with the addition of cranial irradiation starting on day 28 of delayed intensification II chemotherapy.

NOTE: Patients with T-cell disease who are within 4 months of completing delayed intensification I chemotherapy and have not received interim maintenance II chemotherapy with escalating IV methotrexate or delayed intensification II chemotherapy receive a course of interim maintenance chemotherapy and delayed intensification II chemotherapy according to the augmented regimen. If these patients have received interim maintenance II chemotherapy with escalating IV methotrexate, they receive delayed intensification II chemotherapy according to the augmented regimen. These patients also receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy and then proceed to maintenance therapy.

Beginning on day 56 of interim maintenance II chemotherapy, patients receive delayed intensification II chemotherapy as in delayed intensification I chemotherapy.

Beginning on day 56 of delayed intensification II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.

Patients are followed every 4-8 weeks for one year, every 3 months for one year, every 6 months for one year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,037 randomized patients will be accrued for this study within 3.75 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3054
• Est. completion date: June 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 9 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of previously untreated B-cell precursor acute lymphoblastic leukemia

• More than 25% L1 or L2 lymphoblasts

• No more than 25% L3 lymphoblasts

• WBC < 50,000/mm^3

• No T-cell precursor acute lymphoblastic leukemia by immunophenotyping

• Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass allowed

• CNS or testicular leukemia allowed

• No patients found to have t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11-p12;q24) (characteristic of Burkitt's lymphoma)

PATIENT CHARACTERISTICS:

Age:

• 1 to 9

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No more than 72 hours since prior intrathecal cytarabine

Endocrine therapy:

• At least 30 days since prior systemic corticosteroids given for more than 48 hours

• Prior corticosteroids for mediastinal mass causing superior mediastinal syndrome allowed

• Prior or concurrent inhaled corticosteroids allowed

Radiotherapy:

• Prior radiotherapy for mediastinal mass causing superior mediastinal syndrome allowed

• No concurrent spinal radiotherapy

Surgery:

• Not specified

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• cyclophosphamide
Given IV
• cytarabine
Given IT
• daunorubicin hydrochloride
Given IV
• dexamethasone
Given PO
• doxorubicin hydrochloride
Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours
• mercaptopurine
Given PO
• methotrexate
Given PO and IT
• pegaspargase
Given IM
• thioguanine
Given PO
• vincristine sulfate
Given IV

Radiation:
• radiation therapy
Undergo radiation therapy

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Brisbane	Queensland
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Janeway Children's Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
New Zealand	Starship Children's Health	Auckland
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	Texas Tech University Health Sciences Center School of Medicine	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia
United States	Children's Hospital of Austin	Austin	Texas
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Brookdale University Hospital and Medical Center	Brooklyn	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Comprehensive Cancer Center at Maimonides Medical Center	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Children's Hospital Cancer Center	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	St. Mary's - Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Dakota Cancer Institute at Innovis Health - Dakota Clinic	Fargo	North Dakota
United States	Meritcare Roger Maris Cancer Center	Fargo	North Dakota
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	DeVos Children's Hospital	Grand Rapids	Michigan
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	Children's Hospital at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cabell Huntington Hospital	Huntington	West Virginia
United States	Riley Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	East Tennessee State University Cancer Center at Johnson City Medical Center	Johnson City	Tennessee
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Children's Hospitals and Clinics - Minneapolis/St. Paul	Minneapolis	Minnesota
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Children's Hospital of Omaha	Omaha	Nebraska
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	Children's Hospital of Orange County	Orange	California
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Doernbecher Children's Hospital at Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	William Beaumont Hospital - Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente Medical Center - Sacramento	Sacramento	California
United States	MBCCOP - South Texas Pediatrics	San Antonio	Texas
United States	Methodist Cancer Center at Methodist Specialty and Transplant Hospital	San Antonio	Texas
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Deaconess Medical Center	Spokane	Washington
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Long Island Cancer Center at Stony Brook University Hospital	Stony Brook	New York
United States	Valerie Fund Children's Center at Atlantic Health	Summit	New Jersey
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Children's Hospital	Toledo	Ohio
United States	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Switzerland, 

References & Publications (7)

Bruggers CS, Moyer-Mileur LJ, Ransdall L: Body composition, bone mineral acquisition, and cardiovascular fitness in children with standard risk acute lymphoblastic leukemia: response to a home-based exercise and nutrition education program. [Abstract] 2006 Pediatric Academic Societies' Annual Meeting, April 29 - May 2, San Francisco, CA. A-3505.46, 2006.

Fernandez CV, Kodish E, Taweel S, Shurin S, Weijer C; Children's Oncology Group. Disclosure of the right of research participants to receive research results: an analysis of consent forms in the Children's Oncology Group. Cancer. 2003 Jun 1;97(11):2904-9. — View Citation

Matloub Y, Angiolillo A, Bostrom B, et al.: Double delayed intensification (DDI) is equivalent to single DI (SDI) in children with National Cancer Institute (NCI) standard-risk acute lymphoblastic leukemia (SR-ALL) treated on Children's Cancer Group (CCG)

Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.

Matloub Y, Bostrom BC, Angiolillo AL, et al.: Children with NCI standard risk acute lymphoblastic leukemia (ALL) and TEL-AML1 or favorable chromosome trisomies are almost certain to be cured with graduated intensity therapy: results of the CCG - 1991 stud

Matloub Y, Bostrom BC, Hunger SP, et al.: Escalating dose intravenous methotrexate without leucovorin rescue during interim maintenance is superior to oral methotrexate for children with standard risk acute lymphoblastic leukemia (SR-ALL): Children's Onco

Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improve — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	The primary outcome index used in examining the randomized treatment groups will be event free survival (EFS) from the time of randomization (i.e., end of Consolidation), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.	Time of randomization	No