Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103285
• Other study ID #: AALL0331
• Secondary ID: NCI-2009-0030205
• Status: Completed
• Phase: Phase 3
• Start date: April 11, 2005
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5377
• Est. completion date: March 31, 2021
• Est. primary completion date: December 30, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 9 Years

Eligibility

Inclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Childhood B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Radiation:
• 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy

Drug:
• Cyclophosphamide
Given IV
• Cytarabine
Given IV or SC
• Dexamethasone
Given IV or PO
• Doxorubicin Hydrochloride
Given IV or IT
• Leucovorin Calcium
Given PO
• Mercaptopurine
Given PO
• Methotrexate
Given IM or IT
• Pegaspargase
Given IM
• Thioguanine
Given PO
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Children's Hospital-Brisbane	Herston	Queensland
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
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Children's Hospital	London	Ontario
Canada	Victoria 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	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
New Zealand	Wellington Children's Hospital	Wellington
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	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas
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	Emory University Hospital/Winship Cancer Institute	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	Brookdale Hospital Medical Center	Brooklyn	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Maimonides Medical 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	University of Missouri - Ellis Fischel	Columbia	Missouri
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	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
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	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	University of Connecticut	Farmington	Connecticut
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	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	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	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
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	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Care Center	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	University of Kansas Cancer Center	Kansas City	Kansas
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical 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	Valley Children's Hospital	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
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	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	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 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	Sacred Heart Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Oncology Group	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	Rhode Island Hospital	Providence	Rhode Island
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	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	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	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	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Medical Center-Mount Zion	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	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	University of Toledo	Toledo	Ohio
United States	Harbor-University of California at Los Angeles 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
United States	Tod Children's Hospital - Forum Health	Youngstown	Ohio

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 years
Primary	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.	6 years
Secondary	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.	At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
Secondary	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.	MRD at Day 29 of therapy
Secondary	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.	Overall Survival Probability of 6 years
Secondary	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)	Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
Secondary	Optimal Time Point for Advance Health Related Quality of Life Intervention	Percentage of patients with elevated Anxiety.	At 1 month after diagnosis and 3 months post-therapy.
Secondary	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.	6 years
Secondary	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.	6 years

External Links

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