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

April 1, 2022 updated by: Children's Oncology Group

Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

665

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • The Children's Hospital at Westmead
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
      • Herston, Queensland, Australia, 4029
        • Royal Children's Hospital-Brisbane
    • Western Australia
      • Perth, Western Australia, Australia, 6008
        • Princess Margaret Hospital for Children
  • Canada
      • Quebec, Canada, G1V 4G2
        • Centre Hospitalier Universitaire de Quebec
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • British Columbia Children's Hospital
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Children's Hospital at Hamilton Health Sciences
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre
      • London, Ontario, Canada, N6A 5W9
        • Children's Hospital
      • London, Ontario, Canada, N6K 1C2
        • Victoria Hospital
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand, 1145
        • Starship Children's Hospital
  • Puerto Rico
      • San Juan, Puerto Rico, 00912
        • San Jorge Children's Hospital
  • Switzerland
      • Bern, Switzerland, 3010
        • Swiss Pediatric Oncology Group - Bern
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
      • Mobile, Alabama, United States, 36604
        • USA Health Strada Patient Care Center
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
      • Tucson, Arizona, United States, 85724
        • The University of Arizona Medical Center-University Campus
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Long Beach, California, United States, 90806
        • Miller Children's and Women's Hospital Long Beach
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Madera, California, United States, 93636
        • Valley Children's Hospital
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Oakland, California, United States, 94609-1809
        • Children's Hospital and Research Center at Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
      • Torrance, California, United States, 90502
        • Harbor-University of California at Los Angeles Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I duPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Broward Health Medical Center
      • Fort Myers, Florida, United States, 33908
        • Golisano Children's Hospital of Southwest Florida
      • Fort Myers, Florida, United States, 33901
        • Lee Memorial Health System
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Orlando, Florida, United States, 32803
        • Florida Hospital Orlando
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic - Orlando
      • Orlando, Florida, United States, 32806
        • UF Cancer Center at Orlando Health
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Hospital
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
      • Tampa, Florida, United States, 33607
        • Saint Joseph's Hospital/Children's Hospital-Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Mary's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta - Egleston
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61637
        • Saint Jude Midwest Affiliate
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • Saint Vincent Hospital and Health Care Center
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Children's Hospital
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital New Orleans
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Boston, Massachusetts, United States, 02111
        • Floating Hospital for Children at Tufts Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical School
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • C S Mott Children's Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48236
        • Ascension Saint John Hospital
      • East Lansing, Michigan, United States, 48824-7016
        • Michigan State University Clinical Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49008
        • Kalamazoo Center for Medical Studies
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri - Ellis Fischel
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospitals and Clinics
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital and Medical Center of Omaha
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Nevada Cancer Research Foundation CCOP
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Saint Peter's University Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • Saint Joseph's Regional Medical Center
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • Brooklyn, New York, United States, 11201
        • Brooklyn Hospital Center
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, United States, 11040
        • The Steven and Alexandra Cohen Children's Medical Center of New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Mission Hospital Inc-Memorial Campus
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Presbyterian Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43614
        • University of Toledo
      • Toledo, Ohio, United States, 43606
        • The Toledo Hospital/Toledo Children's Hospital
      • Toledo, Ohio, United States, 43608
        • Mercy Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Children's Hospital
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
        • Lehigh Valley Hospital - Muhlenberg
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29605
        • BI-LO Charities Children's Cancer Center
      • Greenville, South Carolina, United States, 29605
        • Greenville Cancer Treatment Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • T C Thompson Children's Hospital
      • Knoxville, Tennessee, United States, 37916
        • East Tennessee Childrens Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Lubbock, Texas, United States, 79410
        • Covenant Children's Hospital
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229
        • Methodist Children's Hospital of South Texas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Vermont
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Portsmouth, Virginia, United States, 23708-2197
        • Naval Medical Center - Portsmouth
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Roanoke, Virginia, United States, 24014
        • Carilion Clinic Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
      • Tacoma, Washington, United States, 98431
        • Madigan Army Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston Division
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Other: Pharmacological Study
Correlative studies
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 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
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamtin
  • Hycamptamine
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)
Drug: Melphalan
Given IV
Other Names:
  • CB-3025
  • L-PAM
  • Alanine Nitrogen Mustard
  • L-Phenylalanine Mustard
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813
  • L-sarcolysin
  • Phenylalanine nitrogen mustard
Biological: Filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
Drug: Vincristine Sulfate Liposome
Given IV
Other Names:
  • Marqibo
Drug: Isotretinoin
Given orally
Other Names:
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
  • 13-cis retinoic acid
  • 13-cis-Retinoate
  • 13-cis-Retinoic Acid
  • 13-cis-Vitamin A Acid
  • 13-cRA
  • Accure
  • Accutane
  • cis-Retinoic Acid
  • Isotretinoinum
  • Isotrex
  • Isotrexin
  • Neovitamin A
  • Neovitamin A Acid
  • Oratane
  • Retinoicacid-13-cis
  • Ro 4-3780
  • Ro-4-3780
  • Roaccutan
  • Roaccutane
  • Roacutan
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
  • PBSCT
  • Peripheral Stem Cell Transplant
EXPERIMENTAL: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Other: Pharmacological Study
Correlative studies
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 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
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamtin
  • Hycamptamine
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)
Drug: Melphalan
Given IV
Other Names:
  • CB-3025
  • L-PAM
  • Alanine Nitrogen Mustard
  • L-Phenylalanine Mustard
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813
  • L-sarcolysin
  • Phenylalanine nitrogen mustard
Biological: Filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
Drug: Thiotepa
Given IV
Other Names:
  • Tepadina
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • WR 45312
  • Triethylene thiophosphoramide
Drug: Vincristine Sulfate Liposome
Given IV
Other Names:
  • Marqibo
Drug: Isotretinoin
Given orally
Other Names:
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret
  • 13-cis retinoic acid
  • 13-cis-Retinoate
  • 13-cis-Retinoic Acid
  • 13-cis-Vitamin A Acid
  • 13-cRA
  • Accure
  • Accutane
  • cis-Retinoic Acid
  • Isotretinoinum
  • Isotrex
  • Isotrexin
  • Neovitamin A
  • Neovitamin A Acid
  • Oratane
  • Retinoicacid-13-cis
  • Ro 4-3780
  • Ro-4-3780
  • Roaccutan
  • Roaccutane
  • Roacutan
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
  • PBSCT
  • Peripheral Stem Cell Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival Rate
Time Frame: Three years, from time of randomization
Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM)
Three years, from time of randomization
Response After Induction Therapy
Time Frame: Study enrollment to the end of induction therapy
Per the International Response Criteria: measurable tumor defined as product of longest x widest perpendicular diameter. Elevated catecholamine levels, tumor cell invasion of bone marrow also considered measurable tumor. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)->90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; >50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by >50%. Mixed Response (MR)->50% reduction of any measurable lesion (primary or metastases) with <50% reduction in other sites; no new lesions; <25% increase in any existing lesion. No Response (NR)-no new lesions; <50% reduction but <25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by >25%; previous negative marrow positive.
Study enrollment to the end of induction therapy
Incidence Rate of Local Recurrence
Time Frame: Up to 3 years
Cumulative incidence rate of local recurrence comparison between ANBL0532 patients randomized or assigned to receive single CEM transplant and boost radiation versus the historical A3973 patients who were transplanted and received boost radiation.
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Greater Than or Equal to Grade 3 Neutropenia
Time Frame: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 39 days
A logistic regression model will be used to test the ability of the number of days of neutropenia to predict the presence of a polymorphism.
Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 39 days
Duration of Greater Than or Equal to Grade 3 Thrombocytopenia
Time Frame: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 46 days
A logistic regression model will be used to test the ability of the number of days of thrombocytopenia to predict the presence of a polymorphism.
Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 46 days
Proportion of Patients With a Polymorphism
Time Frame: Through completion of a participant's first two cycles during induction, including treatment delays, assessed up to 69 days
A chi-square test will be used to test whether the response rate after two cycles of induction therapy and the presence of a polymorphism are independent in the study population.
Through completion of a participant's first two cycles during induction, including treatment delays, assessed up to 69 days
Surgical Response
Time Frame: Up to 3 years
Percentage of patients who achieved a surgical complete resection
Up to 3 years
Type of Surgical or Radiotherapy Complication
Time Frame: Up to 3 years
The Percentage of patients who experienced surgical or radiotherapy complications will be calculated. The complications are: bowel obstruction, chylous leaf, renal injury/atrophy/loss and diarrhea.
Up to 3 years
Intraspinal Extension
Time Frame: Up to 5 years
Percentage of patients with primary tumors with intraspinal extension.
Up to 5 years
Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies
Time Frame: Day 1 of each course
Median peak serum concentration level of isotretinoin for patients enrolled on ANBL0532
Day 1 of each course
Pharmacogenetic Variants in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies
Time Frame: At baseline
To determine if pharmacogenomic variations are predictive of EFS, a logrank test comparison of patients with vs without a given polymorphism will be made. A Fisher's exact test will test for association of the presence of a polymorphism with the occurrence of systemic toxicity (CTC grade 3 or 4 skin, hypercalcemia, or hepatic toxicity). These tests will be performed for UGT1A1, UGT2B7, CYP2C8 and CYP3A7 alleles.
At baseline
Topotecan Systemic Clearance
Time Frame: Day 1 of courses 1-2
Median topotecan systemic clearance for courses 1 and 2.
Day 1 of courses 1-2
Presence and Function of T Cells Capable of Recognizing Neuroblastoma
Time Frame: Up to 6 months (end of therapy)
Up to 6 months (end of therapy)
Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells
Time Frame: Up to 6 months after completion of assigned myeloablation therapy
A descriptive comparison of the median number of T-cells (CD3, CD4, CD8) between treatment arms (single vs. tandem myeloablative regimens) will be performed.
Up to 6 months after completion of assigned myeloablation therapy
Proportion of Patients With Neuroblastoma Detected in Bone Marrow and Peripheral Blood Using RT-PCR Technique
Time Frame: Baseline
Will be calculated overall and by treatment arm.
Baseline
EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology).
Time Frame: Up to 3 years
Kaplan-Meier curves of EFS will be plotted, and the proportion of responders to induction therapy will be tabulated.
Up to 3 years
OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology
Time Frame: Up to 3 years
Kaplan-Meier curves of OS will be plotted, and the proportion of responders to induction therapy will be tabulated.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Julie R Park, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 5, 2007

Primary Completion (ACTUAL)

February 27, 2015

Study Completion (ACTUAL)

March 31, 2022

Study Registration Dates

First Submitted

December 4, 2007

First Submitted That Met QC Criteria

December 4, 2007

First Posted (ESTIMATE)

December 5, 2007

Study Record Updates

Last Update Posted (ACTUAL)

April 28, 2022

Last Update Submitted That Met QC Criteria

April 1, 2022

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANBL0532 (OTHER: CTEP)
  • U10CA180886 (U.S. NIH Grant/Contract)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2009-01065 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000576571
  • 08-524
  • COG-ANBL0532

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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