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Localized Resectable NeuroblastomaPhase 3NCT00033293

Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma

A Phase 3 study testing Clinical Observation, Cyclophosphamide and Laboratory Biomarker Analysis in people with Localized Resectable Neuroblastoma and Localized Unresectable Neuroblastoma, run by Children's Oncology Group at 104 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 8 years
What is being tested?
Clinical Observation, Cyclophosphamide and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
104 sitesin 3 countries
Study dates
15 Mar 2004to 31 Dec 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 8 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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:
Show all 21Show fewer
  • ≤ 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)
  • No prior IV gamma globulin therapy
  • No prior chemotherapy
  • Concurrent chemotherapy allowed
  • No prior prednisone or corticotropin
  • Patients who have received ≤ 14 days of steroids are eligible
  • Concurrent surgery allowed

Who cannot join

None listed.

Trial locations and contacts

104 sites in 3 countries.

104 sites in 3 countries

United States97 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • Texas Tech University Health Sciences Center-Amarillo

    Amarillo, Texas, 79106

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Tufts Children's Hospital

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • West Virginia University Charleston Division

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

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

    Denver, Colorado, 80218

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Michigan State University Clinical Center

    East Lansing, Michigan, 48824-7016

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Greenville Cancer Treatment Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Penn State Children's Hospital

    Hershey, Pennsylvania, 17033

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • Nevada Cancer Research Foundation NCORP

    Las Vegas, Nevada, 89169

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Valley Children's Hospital

    Madera, California, 93636

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Morristown Medical Center

    Morristown, New Jersey, 07960

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

    New Brunswick, New Jersey, 08903

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

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

    New York, New York, 10032

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Legacy Emanuel Hospital and Health Center

    Portland, Oregon, 97227

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Rady Children's Hospital - San Diego

    San Diego, California, 92123

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Overlook Hospital

    Summit, New Jersey, 07902

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

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

    Tampa, Florida, 33607

  • Harbor-University of California at Los Angeles Medical Center

    Torrance, California, 90502

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • New York Medical College

    Valhalla, New York, 10595

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Saint Mary's Hospital

    West Palm Beach, Florida, 33407

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada4 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

Australia3 sites

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6008

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

  • Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

About this study

Official title: A Phase III Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine whether cyclophosphamide and prednisone with or without immune globulin is a reasonable baseline standard therapy for pediatric patients with neuroblastoma-associated opsoclonus-myoclonus-ataxia (OMA) syndrome.

II. Determine whether immunosuppressive therapy with cyclophosphamide and prednisone is an effective backbone therapy for OMA upon which to build additional treatment for these patients

SECONDARY OBJECTIVES:

  1. Determine whether these regimens improve OMA syndrome in these patients. II. Determine whether these regimens improve motor coordination in these patients.

III. Determine these regimens improve functional outcome in these patients. IV. Investigate the biology of neuroblastoma associated OMA, with specific regard to magnetic resonance imaging (MRI) findings, anti-neuronal antibodies, cerebrospinal fluid (CSF) findings and tumor biology.

VI. Define better the long-term prognosis for neurologic recovery in the child with neuroblastoma associated with OMA syndrome. VII. Compare the event-free and overall survival of patients treated with these regimens.

OUTLINE:

CHEMOTHERAPY: Patients 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.

IMMUNE GLOBULIN THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I: 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: 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.

Patients are followed during therapy every month for 6 months, at 1 year, and then annually for up to 10 years.

Being tested
Clinical Observation, Cyclophosphamide, Laboratory Biomarker Analysis, Magnetic Resonance Imaging, Prednisone
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Clinical ObservationOther

    Also called observation

    Undergo observation

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Correlative studies

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given orally

  • Therapeutic Immune GlobulinBiological

    Also called BayGam, Gamimune N, Gamma Globulin, Gammagard S/D

    Given IV

Study groups in NCT00033293
Study groupRoleWhat they receive
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.
Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Drug: Prednisone; Biological: Therapeutic Immune Globulin
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.
Receives: Other: Clinical Observation; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Changes from baseline to 2 months, 6 months, and 1 year

Secondary outcomes (6)

  1. Motor Coordination as Assessed by Neurological Examination and Vineland Adaptive Behavior Scale (VABS)

    The "best" score at the two time points will be used in this analysis. For a given patient, this "best" score will be used to calculate the change from baseline. The mean change from baseline for each treatment group will be calculated.

    Measured: Changes from baseline to the better of 6 months or 1 year

  2. Functional Outcome as Assessed by Age-appropriate Neuropsychological Testing

    The Bayley Scales of infant development mental scale "best" score of two time points will be used in the analysis. For a given patient, this score will be used to calculate the change from baseline.

    Measured: Changes from baseline to the better of 6 months or 1 year

  3. Biology of Neuroblastoma Associated Opsoclonus-myoclonus-ataxia (OMA) Syndrome Specifically by MRI Findings, Anti-neuronal Antibodies, Cerebrospinal Fluid (CSF) Findings and Tumor Biology

    Descriptive analyses on biologic variables will be performed

    Measured: At diagnosis, 6 months, 1 year, 5 and 10 years after diagnosis

  4. Long-term Prognosis for Neurologic Recovery by Neurological Examination

    A t-test will be performed on the results of each neurologic test, comparing patients who have had disappearance of anti-neural antibodies to patients whose anti-neural antibodies have not disappeared.

    Measured: At diagnosis and yearly for 10 years after diagnosis

  5. Tumor Outcome in Terms of Event-free Survival (EFS) Rate Defined as a Relapse or Progression of Neuroblastoma, a Second Malignancy, or Death

    EFS rate for neuroblastoma event from time of study enrollment.

    Measured: Up to 3 years

  6. Tumor Outcome in Terms of Overall Survival (OS) Rate

    OS rate from time of study enrollment.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study start15 Mar 2004
  3. Primary completion10 Dec 2013
  4. Study completion31 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00033293
Sponsor's protocol ID
ANBL00P3
Other IDs
NCI-2009-00399, COG-ANBL00P3, CDR0000069271, ANBL00P3, ANBL00P3, U10CA013539, U10CA180886, U10CA098543
Status last verified
Jan 2023
First submitted
9 Apr 2002
Last updated
18 Apr 2023

Publications

  • 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.

    PubMed 29376112

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clinical Observation, Cyclophosphamide and Laboratory Biomarker Analysis in people with Localized Resectable Neuroblastoma and Localized Unresectable Neuroblastoma, run by Children's Oncology Group at 104 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Responders (time frame: Changes from baseline to 2 months, 6 months, and 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00033293, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.

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