Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma
A Phase III Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone
7 other identifiers
interventional
53
3 countries
104
Brief Summary
This randomized phase III trial is studying cyclophosphamide, prednisone, and immunoglobulin to see how well they work compared to cyclophosphamide and prednisone alone in treating patients with abnormal trunk muscle movements associated with neuroblastoma. Drugs used in chemotherapy, work in different ways to stop tumor cells from dividing so they stop growing or die. Steroid therapy decreases inflammation. Combining chemotherapy and steroid therapy with immunoglobulin may be effective in treating abnormal muscle movement associated with neuroblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Mar 2004
Longer than P75 for phase_3
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 9, 2002
CompletedFirst Posted
Study publicly available on registry
January 27, 2003
CompletedStudy Start
First participant enrolled
March 15, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 10, 2013
CompletedResults Posted
Study results publicly available
October 3, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2022
CompletedApril 18, 2023
January 1, 2023
9.7 years
April 9, 2002
January 28, 2016
March 22, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Responders
A multi-stage design followed by a test of proportions between the treatment arms (chemo vs. chemo + therapeutic immune globulin (IVIG)) will be performed. The first stage of the multi-stage design will also function as an early stopping rule for insufficient activity of chemotherapy in OMA.
Changes from baseline to 2 months, 6 months, and 1 year
Secondary Outcomes (6)
Motor Coordination as Assessed by Neurological Examination and Vineland Adaptive Behavior Scale (VABS)
Changes from baseline to the better of 6 months or 1 year
Functional Outcome as Assessed by Age-appropriate Neuropsychological Testing
Changes from baseline to the better of 6 months or 1 year
Biology of Neuroblastoma Associated Opsoclonus-myoclonus-ataxia (OMA) Syndrome Specifically by MRI Findings, Anti-neuronal Antibodies, Cerebrospinal Fluid (CSF) Findings and Tumor Biology
At diagnosis, 6 months, 1 year, 5 and 10 years after diagnosis
Long-term Prognosis for Neurologic Recovery by Neurological Examination
At diagnosis and yearly for 10 years after diagnosis
Tumor Outcome in Terms of Event-free Survival (EFS) Rate Defined as a Relapse or Progression of Neuroblastoma, a Second Malignancy, or Death
Up to 3 years
- +1 more secondary outcomes
Study Arms (2)
Arm I (chemotherapy, immunoglobulin therapy)
EXPERIMENTALPatients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning on day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 months and then every other day for 7-15 months. Patients receive immune globulin IV on days -2 and -1, at weeks 4, 8, 12, 16, 20, and 24, and then at months 8, 10, and 12 after therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with no response after 6 months go off treatment.
Arm II (chemotherapy, observation)
ACTIVE COMPARATORPatients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning on day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 months and then every other day for 7-15 months. Patients do not receive immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.
Interventions
Undergo observation
Given IV
Correlative studies
Correlative studies
Given orally
Given IV
Eligibility Criteria
You may qualify if:
- Newly diagnosed neuroblastoma (NBL) or ganglioneuroblastoma with tumor-associated opsoclonus-myoclonus-ataxia syndrome (OMA)
- Patients with NBL diagnosed within 6 months of OMA diagnosis AND patients with OMA diagnosed within 6 months of NBL diagnosis are eligible
- Must enroll on study within 4 weeks of diagnosis
- Presence of opsoclonus, myoclonus, and/or ataxia associated with neuroblastoma considered eligible
- Currently enrolled on COG neuroblastoma protocols: COG-ANBL00B1 or its successor
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- ≤ 0.4 mg/dL (for patients 1 to 5 months of age)
- ≤ 0.5 mg/dL (for patients 6 to 11 months of age)
- ≤ 0.6 mg/dL (for patients 1 year of age)
- ≤ 0.8 mg/dL (for patients 2 to 5 years of age)
- ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
- ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
- ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
- ≤ 1.6 mg/dL (for male patients ≥ 16 years of age)
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (104)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Valley Children's Hospital
Madera, California, 93636, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Harbor-University of California at Los Angeles Medical Center
Torrance, California, 90502, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Broward Health Medical Center
Fort Lauderdale, Florida, 33316, United States
Lee Memorial Health System
Fort Myers, Florida, 33901, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504, United States
Sacred Heart Hospital
Pensacola, Florida, 32504, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Saint Mary's Hospital
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Tufts Children's Hospital
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Ascension Saint John Hospital
Detroit, Michigan, 48236, United States
Michigan State University Clinical Center
East Lansing, Michigan, 48824-7016, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503, United States
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Overlook Hospital
Summit, New Jersey, 07902, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Texas Tech University Health Sciences Center-Amarillo
Amarillo, Texas, 79106, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
West Virginia University Charleston Division
Charleston, West Virginia, 25304, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, 6008, Australia
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4, Canada
Related Publications (1)
de Alarcon PA, Matthay KK, London WB, Naranjo A, Tenney SC, Panzer JA, Hogarty MD, Park JR, Maris JM, Cohn SL. Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial. Lancet Child Adolesc Health. 2018 Jan;2(1):25-34. doi: 10.1016/S2352-4642(17)30130-X. Epub 2017 Nov 3.
PMID: 29376112DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Pedro A De Alarcon
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 9, 2002
First Posted
January 27, 2003
Study Start
March 15, 2004
Primary Completion
December 10, 2013
Study Completion
December 31, 2022
Last Updated
April 18, 2023
Results First Posted
October 3, 2016
Record last verified: 2023-01