Clinical trial NCT00381680: Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
Official title: Intensive Treatment for Intermediate-Risk Relapse of Childhood B-precursor Acute Lymphoblastic Leukemia (ALL): A Randomized Trial of Vincristine Strategies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: B-cell Childhood Acute Lymphoblastic Leukemia
L1 Childhood Acute Lymphoblastic Leukemia
L2 Childhood Acute Lymphoblastic Leukemia
Intermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-09-28
Enrollment: 275
Sex: ALL
Minimum age (years): 1
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell 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) and giving the drugs in different ways and different doses may kill more cancer cells..

Detailed description: PRIMARY OBJECTIVES:

I. Determine the efficacy of an intensive chemotherapy regimen (based on POG-9412) for pediatric patients with intermediate-risk relapsed B-precursor acute lymphoblastic leukemia.

SECONDARY OBJECTIVES:

I. To determine levels of minimal residual disease (MRD) present at the end of the first \& third blocks of Induction and determine if higher MRD levels at these times identify patients at higher risk of relapse who might be candidates for alternative therapies in future trials.

II. To determine whether common polymorphisms in candidate genes are associated with the frequency of vincristine adverse effects (peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion \[SIADH\], or constipation) and with anti-leukemic response (level of end-Induction MRD).

III. Compare, descriptively, the outcomes of patients treated with combination chemotherapy vs those treated with matched sibling-related donor hematopoietic stem cell transplantation (for those with eligible donors).

IV. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at initial diagnosis to gain an understanding of the pathways that may be involved in disease resistance.

OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment regimens (randomization closed as of 09/2010).

INDUCTION THERAPY 1 (WEEKS 1-5):

Regimen A: Patients receive low-dose vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) 3 times daily (TID) on days 1-28; doxorubicin hydrochloride IV over 15 minutes on day 1; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; cytarabine intrathecally (IT) on day 1; and methotrexate IT\* on days 15 and 29.

Regimen B: (closed to accrual as of 09/2010)\*\*\*: Patients receive high-dose vincristine IV on days 1, 8, 15, and 22 and prednisone, doxorubicin hydrochloride, pegaspargase, cytarabine, and methotrexate\* as in Regimen A.

NOTE: \*Central nervous system (CNS)-positive patients do not receive methotrexate IT. In both arms, CNS-positive patients receive intrathecal triple therapy (ITT) comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 8, 15, 22, and 29. CNS-positive patients not achieving remission after induction therapy 1 receive one additional dose of ITT on day 36. Patients in both arms then proceed to induction therapy 2\*\*.

NOTE: \*\*Patients who are CNS-positive at relapse receive induction therapy 3 BEFORE induction therapy 2.

NOTE: \*\*\*Patients already enrolled on Regimen B are crossover to Regimen A.

INDUCTION THERAPY 2 (WEEKS 6-10 or 7-11): Once blood counts recover, all patients receive etoposide phosphate IV over = 1 hour and cyclophosphamide IV over 1 hour on days 1-5; high-dose methotrexate IV continuously over 24 hours on day 22; leucovorin calcium IV or PO beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; and methotrexate IT\* on days 1 and 22. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 6 and continuing until blood counts recover.

NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 22. Patients with testicular-relapse with persistent testicular disease at the end of induction therapy 1 undergo testicular radiotherapy once daily (QD), 5 days a week, for 12 days during induction therapy 2\*\*.

NOTE: \*\*Radiotherapy should be completed before beginning high-dose methotrexate (week 9) chemotherapy.

All patients then proceed to induction therapy 3.

INDUCTION THERAPY 3 (WEEKS 11-15 or 12-16): All patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9, and asparaginase IM on days 2 and 9. Patients also receive G-CSF IV or SC beginning on day 10 and continuing until blood counts recover. Patients with a suitable HLA-matched related donor are removed from study and proceed to stem cell transplantation. Patients without a suitable HLA-matched related donor proceed to intensification therapy 1 (as per their randomized regimen in induction therapy 1).

INTENSIFICATION THERAPY 1 (WEEKS 16-27 or 17-28):

Regimen A: Patients receive low-dose vincristine IV and high-dose methotrexate IV continuously over 24 hours on day 1; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 2-6; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 8; and methotrexate IT\* on day 15. Treatment repeats every 21 days for 4 courses (with the exception of IT methotrexate which repeats for only 3 courses).

Regimen B: Patients receive high-dose vincristine IV on day 1 and high-dose methotrexate, leucovorin calcium, mercaptopurine, etoposide phosphate, cyclophosphamide, and methotrexate IT\* as in Regimen A. (closed to accrual as of 09/2010)

NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 15. ITT repeats every 3 weeks for 3 courses.

NOTE: \*\* Patients already enrolled on Regimen B are crossover to Regimen A.

Patients in both regimens then proceed to reinduction therapy (as per their randomized regimen in induction therapy 1).

REINDUCTION THERAPY (WEEKS 28-32 or 29-33):

Regimen A: Patients receive low-dose vincristine IV and doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15, oral dexamethasone twice daily on days 1-7 and 15-21, pegaspargase IM on days 2 and 15, and methotrexate IT\* on days 1 and 28.

Regimen B: Patients receive high-dose vincristine IV on days 1, 8, and 15 and doxorubicin hydrochloride, dexamethasone, pegaspargase, and methotrexate IT\* as in Regimen A. (closed to accrual as of 09/2010)

NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on days 1 and 28.

NOTE: \*\* Patients already enrolled on Regimen B are crossover to Regimen A. Patients in both regimens then proceed to intensification therapy 2 (as per their randomized regimen in induction therapy 1).

INTENSIFICATION THERAPY 2 (WEEKS 33-56 or 34-57):

Regimen A: Once blood counts recover, patients receive high-dose cytarabine IV over 3 hours on days 1 and 2; pegaspargase IM on day 2; low-dose vincristine IV on days 22 and 29; high-dose methotrexate IV on day 22; leucovorin calcium IV or orally beginning 42 hours after start of high-dose methotrexate and continuing every 6 hours for at least 3 doses; oral mercaptopurine once daily on days 23-27; etoposide phosphate IV over ≥ 1 hour and cyclophosphamide IV over 1 hour on day 29; and methotrexate IT\* on day 36. Patients also receive G-CSF IV or SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 42 days for 4 courses (with the exception of IT methotrexate which only repeats for 3 courses).

Regimen B: Patients receive high-dose cytarabine, high-dose methotrexate, leucovorin calcium, pegaspargase, mercaptopurine, etoposide phosphate, cyclophosphamide, methotrexate IT\*, and G-CSF as in Regimen A. Patients also receive high-dose vincristine IV on days 22 and 29.

NOTE: \*CNS-positive patients do not receive methotrexate IT. CNS-positive patients receive ITT on day 36. Treatment repeats every 6 weeks for 3 courses.

Patients in both regimens then proceed to maintenance therapy (as per their randomized regimen in induction therapy 1).

MAINTENANCE THERAPY (week 57-106 or 58-107):

Regimen A: Patients receive methotrexate IT on day 1\* and then PO on days 8, 15, 22, 29, and 36; mercaptopurine PO QD on days 1-42; dexamethasone PO twice daily (BID) on days 1-5; and low-dose vincristine IV and cyclophosphamide IV over 1 hour on days 43, 50, 57, and 64. Treatment repeats every 70 days for 5 courses.

Regimen B: Patients receive methotrexate\*, mercaptopurine, dexamethasone, and cyclophosphamide as in Regimen A. Patients also receive high-dose vincristine IV on days 43, 50, 57, and 64.

NOTE: \*CNS-positive patients receive methotrexate IT on day 1, instead of oral methotrexate.

Beginning in week 1 of the first maintenance therapy course, patients with CNS relapse undergo cranial radiotherapy QD, 5 days a week, for 10 days. Patients with CNS relapse do not receive any IT therapy during maintenance therapy.

After completion of study therapy, patients are followed periodically for 5 years.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acute lymphoblastic leukemia (ALL)

  * Bone marrow with \> 25% L1 or L2 lymphoblasts (M3 marrow)

    * Patients with \> 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are not eligible (considered Burkitt's or mature B-cell leukemia)
* Intermediate-risk relapsed disease, meeting 1 of the following criteria:

  * Bone marrow relapse ≥ 36 months after initial diagnosis (defined as M3 marrow after previous remission from ALL)
  * Combined bone marrow and extramedullary (CNS\* and/or testicular\*\*) relapse ≥ 36 months after initial diagnosis
  * Isolated extramedullary (CNS\* and/or testicular\*\*) relapse \< 18 months after initial diagnosis
* The following subtypes are not allowed:

  * T-lineage ALL
  * Mature B-cell (Burkitt's) leukemia (defined as L3 morphology and/or evidence of c-myc translocation)
  * Philadelphia-chromosome positive disease
* No Down syndrome (trisomy 21)
* Shortening fraction \>= 27% by echocardiogram OR ejection fraction \>= 50% by radionuclide angiogram
* Bilirubin \< 3.0 mg/dL
* Not pregnant
* Fertile patients must use effective contraception
* No history of peripheral neuropathy \>= grade 3 within the past month
* No toxicity (i.e. peripheral neuropathy) \>= grade 3 attributable to vincristine within the past month
* At least 5 days since prior intrathecal chemotherapy
* No prior hematopoietic stem cell or marrow transplantation
* No prior cranial radiotherapy \> 1200 cGy (for patients with CNS relapse)
* No concurrent stem cell transplant
* No concurrent alternative therapy
* No concurrent itraconazole in patients receiving vincristine
* No concurrent intensity-modulated radiotherapy

Primary outcomes:
measure: Event Free Survival. EFS
timeFrame: 3 years after enrollment
Secondary outcomes:
measure: Frequency and Severity of Adverse Effects
timeFrame: Up to 107 weeks
measure: Gene Expression Profile
timeFrame: Up to 36 months
measure: Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1
timeFrame: End of Block 1 (35 days) of Induction therapy
measure: Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3
timeFrame: End of Block 3 (105 days) of Induction therapy
measure: Event Free Survival (EFS)
timeFrame: 3 years
measure: Adjusted Event Free Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Childrens Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: Sacramento
country: United States
facility: Sutter General Hospital
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Parnassus
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Orlando
country: United States
facility: M D Anderson Cancer Center- Orlando
state: Florida
city: Orlando
country: United States
facility: Nemours Childrens Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph Children's Hospital of Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Boise
country: United States
facility: Saint Luke's Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Hope Children's Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Services
state: Indiana
city: Des Moines
country: United States
facility: Raymond Blank Children's Hospital
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital-Main Campus
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Center for Medical Studies
state: Michigan
city: Lansing
country: United States
facility: Michigan State University - Breslin Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri-Columbia
state: Missouri
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson University Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospitals Inc
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: The Children's Medical Center of Dayton
state: Ohio
city: Toledo
country: United States
facility: Mercy Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Greenville
country: United States
facility: BI-LO Charities Children's Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Treatment Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Chattanooga
country: United States
facility: T C Thompson Children's Hospital
state: Tennessee
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Science Center-Amarillo
state: Texas
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Childrens Hospital-King's Daughters
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic Children's Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital and Health Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Charleston
country: United States
facility: West Virginia University Charleston
state: West Virginia
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Hamilton
country: Canada
facility: Chedoke-McMaster Hospitals
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: Hospital Sainte-Justine
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Bern
country: Switzerland
facility: Swiss Pediatric Oncology Group - Bern
city: Lausanne
country: Switzerland
facility: Swiss Pediatric Oncology Group - Lausanne
Study officials:
affiliation: Children's Oncology Group
name: Glen Lew, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2021 Jan 1;106(1):46-55. doi: 10.3324/haematol.2019.237230.