Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma

NCT ID: NCT00567567

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 665 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-05
• Study Completion Date: 2022-03-31

Brief Summary

This randomized phase III trial compares two different high-dose chemotherapy regimens followed by a stem cell transplant in treating younger patients with high-risk neuroblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments before a peripheral blood stem cell transplant helps kill any tumor cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. High-dose chemotherapy and radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the high- chemotherapy. It is not yet known which regimen of high-dose chemotherapy is more effective for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.

Detailed Description

PRIMARY OBJECTIVES:

I. To improve the 3-year event-free survival (EFS) rate of high-risk neuroblastoma patients through treatment with a tandem consolidation of thiotepa/cyclophosphamide followed by carboplatin/etoposide/melphalan (CEM) as compared to single CEM consolidation.

II. To improve the rate of end-induction complete response and very good partial response, compared to historical controls, by use of a topotecan-containing induction regimen.

III. To improve the 3-year local control rate, compared to historical controls, by increasing the local dose of radiation to the residual primary tumor for patients with less than a gross total resection.

SECONDARY OBJECTIVES:

I. To evaluate the pharmacogenetic relationship of cyclophosphamide metabolizing enzymes (CYP2B6, CYP2C9, and GSTA1 genotypes) with toxicity and response following dose-intensive cyclophosphamide and topotecan induction chemotherapy.

II. To determine if resection completeness is predictive of a) local control rate; or b) EFS rate in patients with high-risk neuroblastoma.

III. To prospectively describe the complications related to efforts at local control (surgery and radiation therapy) in patients with high-risk neuroblastoma.

IV. To describe the neurologic outcome of patients with paraspinal primary neuroblastoma tumors.

V. To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters and determine if pharmacokinetics and/or genetic variations correlate with EFS or systemic toxicity as follows: a) To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters. b) To determine if 13-cis-retinoic-acid pharmacokinetic levels are predictive of the EFS rate or associated with systemic toxicity following 13-cis-retinoic acid. c) To determine if pharmacogenomic variations are predictive of the EFS rate or associated with systemic toxicity following 13-cis-retinoic acid.

VI. To evaluate total topotecan pharmacokinetics and correlate with patient specific data for use in an ongoing topotecan population pharmacokinetic analysis.

VII. To evaluate the presence and function of T cells capable of recognizing neuroblastoma by assessing: a) if T cells recognizing the neuroblastoma antigen, survivin, circulate at diagnosis; b) if these T cells can be expanded using autologous antigen presenting cells (APCs); c) if these T cells will kill neuroblastoma cells as detected in functional assays; and d) if the presence and activity of anti-neuroblastoma immunity is decreased by stem cell transplantation.

VIII. To characterize the recovery of T- cell numbers after myeloablative consolidation and hematopoietic stem cell transplant (HSCT) and assess the impact of tandem myeloablative consolidation on T- cell recovery.

IX. To characterize minimal residual disease burden using reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation of a panel of neuroblastoma specific transcripts in patient bone marrow and peripheral blood following induction chemotherapy and after single versus tandem myeloablative chemotherapy and to evaluate impact on EFS.

X. To evaluate the EFS and overall survival (OS) rate for patients 12-18 months with Stage 4, MYCN nonamplified tumor with unfavorable histopathology or diploid DNA content or with indeterminant histology or ploidy and patients who are greater than 547 days of age with Stage 3, MYCN nonamplified tumor AND unfavorable histopathology or indeterminant histology following treatment with single myeloablative transplant.

OUTLINE:

INDUCTION CHEMOTHERAPY:

COURSES 1 AND 2: Patients receive cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients undergo peripheral blood stem cell (PBSC) mobilization and harvest after course 2.

COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4, etoposide IV over 1 hour on days 1-3, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients undergo surgical resection of soft tissue disease after course 5 (or after course 6 if medically necessary).

COURSES 4 AND 6: Patients receive cyclophosphamide IV over 6 hours on days 1-2, doxorubicin hydrochloride IV over 24 hours on days 1-3, vincristine IV on days 1-3, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses.

Patients are then stratified by initial stage of disease and MYCN status, biologic characteristics, and response to induction chemotherapy (complete response/very good partial response vs partial response vs mixed response/no response). Patients are randomized to 1 of 2 arms. Patients 12?18 months old (i.e., 365-547 days) with stage IV, MYCN nonamplified tumor with unfavorable histopathology or diploid DNA content or with indeterminant histology or ploidy AND patients who are 547 days of age with stage III, MYCN nonamplified tumor AND unfavorable histopathology or indeterminant histology will be nonrandomly assigned to Arm A. Patients begin consolidation chemotherapy no later than 8 weeks after the start of induction course 6.

CONSOLIDATION THERAPY:

ARM A (single myeloablative consolidation): Patients receive melphalan IV over 15-30 minutes on days -7 to -5, etoposide IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Patients undergo autologous peripheral blood stem cell transplant (PBSCT) on day 0.

ARM B (tandem myeloablative consolidation): Patients receive thiotepa IV over 2 hours on days -7 to -5, cyclophosphamide IV over 1 hour on days -5 to -2, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Following clinical recovery from initial myeloablative therapy, patients also receive melphalan, etoposide, and carboplatin as in Arm A. Patients undergo autologous PBSCT on day 0.

RADIOTHERAPY: Patients undergo external beam radiation therapy (EBRT) to primary site of disease as well as to MIBG-avid sites seen at pre-transplantation (i.e., end-induction) evaluation between 28-42 days post-transplant. Additional radiotherapy is administered to residual tumor at primary site.

MAINTENANCE THERAPY: Patients are encouraged to enroll onto Children?s Oncology Group (COG)-ANBL0032 following assessment of tumor response after completion of the consolidation phase and radiotherapy. Beginning on day 60 post-transplantation patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood and tissue sample collection periodically for the following analyses; correlation between peak serum concentration level and the existence of polymorphisms, event-free survival, and toxicity rates; pharmacogenomics for uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), UGT2B7, CYP2C8 and CYP3A7 alleles; topotecan systemic clearance; survivin-specific cytotoxic T-lymphocytes (CTLs) detected using peptide/major histocompatibility complex (MHC) tetramers in human leukocyte antigen (HLA)-A2+ patients; interferon (IFN)-gamma production in enzyme-linked immunospot (ELISPOT) assays to APCs loaded with tumor ribonucleic acid (RNA), survivin RNA, or control RNA; response of APC-stimulated CTL response to neuroblastoma cells; rate of T cell recovery; and proportion of patients with neuroblastoma detected in bone marrow and peripheral blood using RT-PCR and immunohistochemistry (IHC).

After completion of study treatment, patients are followed up periodically for 5 years and then annually for 5 years.

Conditions

Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Recurrent Neuroblastoma; Regional Neuroblastoma; Stage 4 Neuroblastoma; Stage 4S Neuroblastoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Consolidation Arm A: single myeloablative consolidation

Patients receive melphalan IV over 15-30 minutes on days -7 to -5, etoposide IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Patients undergo autologous PBSCT on day 0.

Group Type: ACTIVE_COMPARATOR

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Carboplatin

Intervention Type: DRUG

Given IV

Cisplatin

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

External Beam Radiation Therapy

Intervention Type: RADIATION

Undergo EBRT

Filgrastim

Intervention Type: BIOLOGICAL

Given IV or SC

Isotretinoin

Intervention Type: DRUG

Given orally

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Melphalan

Intervention Type: DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Topotecan Hydrochloride

Intervention Type: DRUG

Given IV

Vincristine Sulfate Liposome

Intervention Type: DRUG

Given IV

Consolidation Arm B: tandem myeloablative consolidation

Patients receive thiotepa IV over 2 hours on days -7 to -5, cyclophosphamide IV over 1 hour on days -5 to -2, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Following clinical recovery from initial myeloablative therapy, patients also receive melphalan, etoposide, and carboplatin as in Arm A. Patients undergo autologous PBSCT on day 0.

Group Type: EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Carboplatin

Intervention Type: DRUG

Given IV

Cisplatin

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

External Beam Radiation Therapy

Intervention Type: RADIATION

Undergo EBRT

Filgrastim

Intervention Type: BIOLOGICAL

Given IV or SC

Isotretinoin

Intervention Type: DRUG

Given orally

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Melphalan

Intervention Type: DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Thiotepa

Intervention Type: DRUG

Given IV

Topotecan Hydrochloride

Intervention Type: DRUG

Given IV

Vincristine Sulfate Liposome

Intervention Type: DRUG

Given IV

Interventions

Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Carboplatin

Given IV

Intervention Type: DRUG

Cisplatin

Given IV

Intervention Type: DRUG

Cyclophosphamide

Given IV

Intervention Type: DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Etoposide

Given IV

Intervention Type: DRUG

External Beam Radiation Therapy

Undergo EBRT

Intervention Type: RADIATION

Filgrastim

Given IV or SC

Intervention Type: BIOLOGICAL

Isotretinoin

Given orally

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Melphalan

Given IV

Intervention Type: DRUG

Peripheral Blood Stem Cell Transplantation

Undergo autologous peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Thiotepa

Given IV

Intervention Type: DRUG

Topotecan Hydrochloride

Given IV

Intervention Type: DRUG

Vincristine Sulfate Liposome

Given IV

Intervention Type: DRUG

Other Intervention Names

Autologous Hematopoietic Cell Transplantation; autologous stem cell transplantation; Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Abiplatin; Blastolem; Briplatin; CDDP; Cis-diammine-dichloroplatinum; Cis-diamminedichloridoplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cismaplat; Cisplatina; Cisplatinum; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Neoplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Definitive Radiation Therapy; EBRT; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; FILGRASTIM, LICENSE HOLDER UNSPECIFIED; G-CSF; Neupogen; r-metHuG-CSF; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; 13-cis retinoic acid; 13-cis-Retinoate; 13-cis-Retinoic Acid; 13-cis-Vitamin A Acid; 13-cRA; Accure; Accutane; Amnesteem; cis-Retinoic Acid; Cistane; Claravis; Isotretinoinum; Isotrex; Isotrexin; Neovitamin A; Neovitamin A Acid; Oratane; Retinoicacid-13-cis; Ro 4-3780; Ro-4-3780; Roaccutan; Roaccutane; Roacutan; Sotret; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine nitrogen mustard; Sarcoclorin; Sarkolysin; WR-19813; PBPC transplantation; PBSCT; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation; 1,1',1''-Phosphinothioylidynetrisaziridine; Girostan; N,N', N''-Triethylenethiophosphoramide; Oncotiotepa; STEPA; Tepadina; TESPA; Tespamin; Tespamine; Thio-Tepa; Thiofosfamide; Thiofozil; Thiophosphamide; Thiophosphoramide; Thiotef; Tifosyl; TIO TEF; Tio-tef; Triethylene thiophosphoramide; Triethylenethiophosphoramide; Tris(1-aziridinyl)phosphine sulfide; TSPA; WR 45312; Hycamptamine; Hycamtin; SKF S-104864-A; Topotecan HCl; topotecan hydrochloride (oral); Marqibo

Eligibility Criteria

Inclusion Criteria

• Diagnosis of neuroblastoma or ganglioneuroblastoma by histology or as evidenced by the presence of clumps of tumor cells in bone marrow and elevated catecholamine metabolites in urine meeting any of the following criteria:

• Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 disease are eligible with the following:

• MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
• Age > 18 months (i.e., > 547 days) regardless of biologic features
• Age 12-18 months (i.e., 365-547 days) with none of the following three favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1)
• Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:

• MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
• Age > 18 months (i.e., > 547 days) with unfavorable pathology, regardless of MYCN status
• Patients with newly diagnosed INSS stage 2a or 2b with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
• Patients with newly diagnosed INSS stage 4s with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features
• Patients >= 365 days initially diagnosed with INSS stage 1, 2, or 4S and who progressed to a stage 4 without interval chemotherapy

• Must have been enrolled on COG-ANBL00B1
• Creatinine clearance or radioisotope glomerular filtration rate ? 70mL/min OR serum creatinine based on age/gender as follows:

• 1 month to < 6 months: 0.4 mg/dL
• 6 months to < 1 year: 0.5 mg/dL
• 1 to < 2 years: 0.6 mg/dL
• 2 to < 6 years: 0.8 mg/dL
• 6 to < 10 years: 1 mg/dL
• 10 to < 13 years: 1.2 mg/dL
• 10 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
• Total bilirubin ? 1.5 times upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 10 times ULN for age
• Not pregnant or nursing
• Negative pregnancy test
• Shortening fraction >= 27% by echocardiogram (ECHO) OR left ventricular ejection fraction (LVEF) >= 50% by radionuclide angiogram
• No known contraindication (e.g., size, weight or physical condition) to peripheral blood stem cell collection
• No prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease
• No more than one course of chemotherapy per low- or intermediate-risk neuroblastoma therapy prior to determination of MYCN amplification and histology

• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie R Park

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

The University of Arizona Medical Center-University Campus

Tucson, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, 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

Children's Hospital Los Angeles

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, 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

Harbor-University of California at Los Angeles Medical Center

Torrance, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

University of Connecticut

Farmington, Connecticut, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Lee Memorial Health System

Fort Myers, Florida, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Florida Hospital Orlando

Orlando, Florida, United States

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

UF Cancer Center at Orlando Health

Orlando, Florida, United States

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Sacred Heart Hospital

Pensacola, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Saint Mary's Hospital

West Palm Beach, Florida, 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

Memorial Health University Medical Center

Savannah, Georgia, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, 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

Blank Children's Hospital

Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Norton Children's Hospital

Louisville, Kentucky, United States

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Eastern Maine Medical Center

Bangor, Maine, United States

Maine Children's Cancer Program

Scarborough, Maine, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Ascension Saint John Hospital

Detroit, Michigan, United States

Michigan State University Clinical Center

East Lansing, Michigan, United States

Hurley Medical Center

Flint, Michigan, 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

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Kalamazoo Center for Medical Studies

Kalamazoo, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Morristown Medical Center

Morristown, New Jersey, United States

Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Overlook Hospital

Summit, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Albany Medical Center

Albany, New York, United States

Brooklyn Hospital Center

Brooklyn, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Mount Sinai Hospital

New York, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

New York Medical College

Valhalla, New York, United States

Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Dayton Children's Hospital

Dayton, Ohio, United States

The Toledo Hospital/Toledo Children's Hospital

Toledo, Ohio, United States

Mercy Children's Hospital

Toledo, Ohio, United States

University of Toledo

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 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

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Prisma Health Richland Hospital

Columbia, South Carolina, United States

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Greenville Cancer Treatment Center

Greenville, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Driscoll Children's Hospital

Corpus Christi, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Covenant Children's Hospital

Lubbock, 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

Primary Children's Hospital

Salt Lake City, Utah, United States

University of Vermont and State Agricultural College

Burlington, Vermont, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Carilion Clinic Children's Hospital

Roanoke, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Madigan Army Medical Center

Tacoma, Washington, United States

West Virginia University Charleston Division

Charleston, West Virginia, United States

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Royal Children's Hospital-Brisbane

Herston, Queensland, Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Alberta Children's Hospital

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, 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

Victoria Hospital

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Starship Children's Hospital

Grafton, Auckland, New Zealand

San Jorge Children's Hospital

San Juan, , Puerto Rico

Swiss Pediatric Oncology Group - Bern

Bern, , Switzerland

Countries

United States; Australia; Canada; New Zealand; Puerto Rico; Switzerland

References

Berko ER, Naranjo A, Daniels AA, McNulty SN, Krytska K, Druley T, Zelley K, Koneru B, Chen L, Polkosnik G, Irwin MS, Bagatell R, Maris JM, Reynolds CP, DuBois SG, Park JR, Mosse YP. Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study. J Clin Oncol. 2025 May 10;43(14):1673-1684. doi: 10.1200/JCO-24-02407. Epub 2025 Mar 4.

Reference Type: DERIVED

PMID: 40036726 (View on PubMed)

Liu KX, Naranjo A, Zhang FF, DuBois SG, Braunstein SE, Voss SD, Khanna G, London WB, Doski JJ, Geiger JD, Kreissman SG, Grupp SA, Diller LR, Park JR, Haas-Kogan DA. Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children's Oncology Group ANBL0532 Study. J Clin Oncol. 2020 Aug 20;38(24):2741-2752. doi: 10.1200/JCO.19.03316. Epub 2020 Jun 12.

Reference Type: DERIVED

PMID: 32530765 (View on PubMed)

Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. JAMA. 2019 Aug 27;322(8):746-755. doi: 10.1001/jama.2019.11642.

Reference Type: DERIVED

PMID: 31454045 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://nctn-data-archive.nci.nih.gov/

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

Other Identifiers

NCI-2009-01065

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000576571

Identifier Type: -

Identifier Source: secondary_id

08-524

Identifier Type: -

Identifier Source: secondary_id

COG-ANBL0532

Identifier Type: -

Identifier Source: secondary_id

ANBL0532

Identifier Type: OTHER

Identifier Source: secondary_id

ANBL0532

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ANBL0532

Identifier Type: -

Identifier Source: org_study_id