Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Treatment of Patients With Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-Lineage Lymphoblastic Lymphoma (B-LLy)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01190930
• Other study ID #: AALL0932
• Secondary ID: NCI-2011-02599CD
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 9, 2010
• Est. completion date: March 31, 2028

Study information

• Verified date: February 2024
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This partially randomized phase III trial studies the side effects of different combinations of risk-adapted chemotherapy regimens and how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

l. To determine if a maintenance regimen containing weekly oral methotrexate at 40 mg/m^2/week will result in an improved disease free survival (DFS) compared to that containing weekly oral methotrexate at 20 mg/m^2/week in the average-risk (AR) subset of patients with standard-risk B-precursor acute lymphoblastic leukemia (ALL). (Complete effective January 13, 2017) II. To determine whether a reduced-pulses maintenance regimen with vincristine (vincristine sulfate)/dexamethasone pulses delivered every 12 weeks can be used without adversely impacting DFS as compared to pulses given every 4 weeks in the AR subset of patients with standard risk B-precursor ALL.

III. To confirm that patients in the low-risk (LR) subset of standard risk B-precursor ALL, based on clinical and cytogenetic features and minimal residual disease (MRD) criteria, can attain a 5 year DFS of at least 95% with either a P9904 based regimen that includes 6 courses of intermediate dose (1 g/m^2 over 24 hours) methotrexate without alkylating agents or anthracyclines (Arm LR-M), or an outpatient based regimen identical to that of AR patients with reduced vincristine/dexamethasone pulses at 12 week intervals during maintenance (Arm LR-C).

IV. To provide standardized treatment and enhanced supportive care to children with standard-risk (SR) Down syndrome B-ALL in order to improve outcomes and facilitate further study of this biologically and clinically unique patient subgroup.

V. To improve understanding of the biology of localized B-lineage lymphoblastic lymphoma (B-LLy) and Down syndrome (DS) B-LLy by obtaining biologic data, including fluorescence in situ hybridization (FISH) for recurrent cytogenetic lesions on paraffin specimen, and banking tissue for future research.

VI. To describe the 5-year event free survival (EFS) and overall survival (OS) of patients with Murphy stage I and II B-LLy receiving modified AR B-ALL therapy.

SECONDARY OBJECTIVES:

I. To assess the burden of AR B-ALL therapy as measured by surveys of the child's quality of life, missed days of school/daycare/work by children and parents, family functioning, parental perception of the child's health vulnerability, physical functioning, and emotional distress, 1) overall at different time points during and at the end of therapy, and by 2) comparing children randomized to every 4 week vs. every 12 week dexamethasone/vincristine pulses during maintenance. (Closed to accrual as of April 19, 2013) II. To characterize the onset, severity, and natural history of vincristine associated neuropathy by physical therapists (or occupational therapists) in children undergoing therapy for AR B-ALL, 1) overall at different time points during and at the end of therapy, and by 2) comparing children randomized to every 4 week vs. every 12 week dexamethasone/vincristine pulses during maintenance. (Closed to accrual as of March 15, 2013)

TERTIARY OBJECTIVES:

I. To explore the correlation of minimal marrow disease (MMD) at diagnosis and outcome for patients with B-LLy. (Closed effective Amendment #5)

OUTLINE:

All patients receive induction therapy comprising intrathecal (IT) cytarabine on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-28; pegaspargase IV over 1-2 hours on day 4; and IT methotrexate* on days 8 and 29. Patients with Philadelphia chromosome-positive disease are eligible to transfer to COG-AALL0622 by day 15 of induction therapy and patients with high-risk (HR) or very high-risk (VHR) disease are eligible to transfer to a COG HR or VHR trial at the end of induction therapy. Patients with standard-risk disease with Down syndrome (DS) who have bone marrow minimal residual disease 0.01% are eligible to transfer to the DS stratum of the HR trial. Patients with induction failure (defined as M3 [> 25% lymphoblasts] on day 29) may be eligible for the COG VHR-acute lymphoblastic leukemia study.

NOTE: *Patients with DS also receive oral leucovorin calcium every 12 hours on days 10-11 and 31-32.

STANDARD-RISK WITH DOWN SYNDROME:

Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; IT methotrexate on days 1, 8, and 15; and leucovorin calcium PO every 12 hours on days 3-4, 10-11, and 17-18. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on day 31; and leucovorin calcium PO every 12 hours on days 36-34. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 33-39; IT methotrexate on days 1 and 29; and leucovorin calcium PO every 12 hours on days 3-4 and 31-32. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on days 1 and 31; and leucovorin calcium PO every 12 hours on days 3-4 and 33-34. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 12 weeks for 2 years (timed from the start of interim maintenance I therapy).

B-LLy:

Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; IT methotrexate on days 1, 8, and 15; and leucovorin calcium PO every 12 hours on days 3-4, 10-11, and 17-18. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on day 31; and leucovorin calcium PO every 12 hours on days 36-34. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 33-39; IT methotrexate on days 1 and 29; and leucovorin calcium PO every 12 hours on days 3-4 and 31-32. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on days 1 and 31; and leucovorin calcium PO every 12 hours on days 3-4 and 33-34. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 4 weeks for 2 years (timed from the start of interim maintenance I therapy).

AVERAGE-RISK:

Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; and IT methotrexate on days 1, 8, and 15.Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31. Delayed intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and IT methotrexate on days 1 and 29. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31. Maintenance therapy: Patients are randomized to 1 of 4 maintenance therapy treatment arms.

Arm A: Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Arm B: Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Arm C: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

Arm D: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.

In all arms, maintenance therapy courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy).

LOW-RISK: Patients are randomized to 1 of 2 treatment arms.

Arm I (LR-M): Consolidation therapy (19 weeks): Beginning one week after completion of induction therapy, patients receive vincristine sulfate IV on days 15, 22, 78, and 85; methotrexate IV over 24 hours and IT methotrexate on days 8, 29, 50, 71, 92, and 113; leucovorin calcium PO or IV on days 9-10, 30-31, 51-52, 72-73, 93-94, and 114-115; dexamethasone PO BID or IV on days 15-21 and 78-84; and PO mercaptopurine on days 1-133.Maintenance therapy: Patients receive vincristine sulfate IV on days 1 and 8; dexamethasone PO BID on days 1-7; methotrexate* PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106; and mercaptopurine PO on days 1-112. Courses repeat every 16 weeks. Patients also receive IT methotrexate on days 1 and 85 (courses 1 and 4), day 57 (courses 2 and 5), or day 29 (courses 3 and 6). Patients then receive course 7 comprising vincristine sulfate IV on days 1 and 8; dexamethasone PO BID on days 1-7; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64; and mercaptopurine PO on days 1-70. Treatment continues for 2 and ½ years (timed from the date of diagnosis).NOTE: *Patients do not receive methotrexate PO on the days that they receive IT methotrexate.

Arm II (LR-C): Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; oral mercaptopurine on days 1-28; and IT methotrexate on days 1, 8, and 15. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and IT methotrexate on days 1 and 29.Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy).

After completion of study treatment, patients are followed up periodically for 10 years from study entry.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9350
• Est. completion date: March 31, 2028
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

Inclusion Criteria:

• B-ALL patients must be enrolled on AALL08B1 or APEC14B1 (if open for the classification of newly diagnosed ALL patients) prior to treatment and enrollment on AALL0932

• Note: B-LLy patients are not eligible for AALL08B1, and can enroll directly onto AALL0932

• B-ALL patients must have an initial white blood cell count < 50,000/uL

• Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible

• Note: for B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met

Exclusion Criteria:

• With the exception of steroid pretreatment (defined below) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL0932

• Patients receiving prior steroid therapy may be eligible for AALL0932

• Patients with central nervous system 3 (CNS3) leukemia

• CNS status must be known prior to enrollment; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); B-LLy patients with CNS3 disease are not eligible for this protocol or the COG HR ALL protocol; it is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; this is allowed prior to registration; systemic chemotherapy must begin within 72 hours of the first dose of intrathecal therapy

• B-ALL patients with testicular leukemia are not eligible for AALL0932

• For B-LLy patients the following additional exclusion criteria apply:

• T-lymphoblastic lymphoma

• Morphologically unclassifiable lymphoma

• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma

• CNS3-positive disease or testicular involvement

• M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow

• Female patients who are pregnant are ineligible

• Lactating females are not eligible unless they have agreed not to breastfeed their infants

• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult B Lymphoblastic Lymphoma
• Ann Arbor Stage I B Lymphoblastic Lymphoma
• Ann Arbor Stage II B Lymphoblastic Lymphoma
• Childhood B Acute Lymphoblastic Leukemia
• Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Childhood B Lymphoblastic Lymphoma
• Down Syndrome
• Hypodiploid B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Philadelphia Chromosome
• Philadelphia Chromosome Positive
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Cyclophosphamide
Given IV
• Cytarabine
Given IT, IV, or SC
• Dexamethasone
Given orally (PO) or IV
• Doxorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Leucovorin Calcium
Given PO
• Mercaptopurine
Given PO
• Methotrexate
Given IT, PO, or IV
• Pegaspargase
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Drug:
• Thioguanine
Given PO
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
Australia	Monash Medical Center-Clayton Campus	Clayton	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Children's Hospital-Brisbane	Herston	Queensland
Australia	John Hunter Children's Hospital	Hunter Regional Mail Centre	New South Wales
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	Queensland Children's Hospital	South Brisbane	Queensland
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Children's Hospital	London	Ontario
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Ireland	Our Lady's Children's Hospital	Dublin	Co Dublin
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
Puerto Rico	San Jorge Children's Hospital	San Juan
Puerto Rico	University Pediatric Hospital	San Juan
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	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Children's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Columbia Regional	Columbia	Missouri
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	El Paso Children's Hospital	El Paso	Texas
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's and Women's Hospital Long Beach	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Mattel Children's Hospital UCLA	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	UMC Cancer Center / UMC Health System	Lubbock	Texas
United States	Valley Children's Hospital	Madera	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Vannie Cook Children's Clinic	McAllen	Texas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Banner Children's at Desert	Mesa	Arizona
United States	Miami Cancer Institute	Miami	Florida
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	USA Health Strada Patient Care Center	Mobile	Alabama
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	The Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Weill Cornell Medical Center	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	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Carilion Children's	Roanoke	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Naval Medical Center -San Diego	San Diego	California
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Mercy Children's Hospital	Toledo	Ohio
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  New Zealand,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival (DFS) in Average Risk (AR) Patients Based on the Methotrexate Dose Randomization	DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.	5.7 years
Primary	DFS in Average Risk (AR) Patients Based on the Pulse Frequency Randomization	DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.	5.7 years
Primary	DFS in Low Risk (LR) Patients Based on Randomization to 1 of 2 Low-intensity Regimens	DFS is calculated as the time from randomization at the end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.	5.1 years
Primary	DFS for SR Down Syndrome Patients With Standardized Treatment and Enhanced Supportive Care	DFS is calculated as the time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. The 5-year DFS and 95% confidence interval for these patients will be estimated.	5.1 years
Primary	Sample Collection of Central Path Review Slides in B-LLy Patients	Percent of B-LLy patients who had adequate/usable samples of samples collected will be reported.	Up to 1 month
Primary	Event Free Survival (EFS) for B-LLy Patients	EFS is calculated as the Time from study enrollment to first event (induction failure, relapse, second malignancy, remission death) or date of last contact. The 5-year EFS and 95% confidence interval for these patients will be estimated.	5 years
Primary	Overall Survival (OS) for B-LLy Patients	OS is calculated as the time from study enrollment to death or date of last contact. The 5-year OS and 95% confidence interval for these patients will be estimated.	5 years
Secondary	Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2 Months
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1 year
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1.7 years
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2.5 years
Secondary	Burden of Therapy in Boy AR Patients Overall at End of Therapy: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Genetic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	3.2 years
Secondary	Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Physical	Age and gender standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2 Months
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1 Year
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1.7 years
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients Overall at End of Therapy: Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	3.2 years
Secondary	Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2 Months
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1 Year
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1.7 Years
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2.4 years
Secondary	Burden of Therapy in Boy AR Patients Overall at End of Therapy: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	3.2 Years
Secondary	Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2 Months
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1 Year
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	1.7 Years
Secondary	Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients Overall at End of Therapy: Social Functioning	Age standardized Quality of life, measured by the Social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.	3.2 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.	1.7 years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Emotional	Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	3.2 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.	1.7 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Physical	Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	3.2 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.	1.7 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: School	Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	3.2 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.	1.7 Years
Secondary	Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	2.4 Years
Secondary	Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Social Functioning	Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.	3.2 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Right	Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	2 Months
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Left	Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	2 Months
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Right	Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	1 Year
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Left	Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	1 Year
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right	Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	2.4 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left	Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	2.4 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Right	Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	4.2 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Left	Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.	4.2 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right	Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported.	2.4 Years
Secondary	Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left	Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported.	2.4 Years

External Links

•   Available IPD/Information: Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive