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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00033293




Registration number
NCT00033293
Ethics application status
Date submitted
9/04/2002
Date registered
27/01/2003
Date last updated
22/05/2017

Titles & IDs
Public title
Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma
Scientific title
A Pilot Study Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone
Secondary ID [1] 0 0
NCI-2009-00399
Secondary ID [2] 0 0
ANBL00P3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Disseminated Neuroblastoma 0 0
Localized Resectable Neuroblastoma 0 0
Localized Unresectable Neuroblastoma 0 0
Regional Neuroblastoma 0 0
Stage 4S Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - therapeutic immune globulin
Other interventions - clinical observation
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - prednisone
Treatment: Surgery - magnetic resonance imaging
Other interventions - laboratory biomarker analysis
Treatment: Drugs - Corticotropin-Releasing Hormone

Experimental: Arm I (chemotherapy, immunoglobulin therapy) - 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 day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hr on day 0. Treatment repeats every 4 wks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 mths and then every other day for 7-15 mths.
Patients receive therapeutic immune globulin IV on days -2 and -1, at wks 4, 8, 12, 16, 20, and 24, and then at mths 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. In case of progression of opsoclonus-myoclonus-ataxia (OMA) during evaluation, patient will be switched to another steroid, corticotropin-releasing hormone (ACTH).

Active Comparator: Arm II (chemotherapy, observation) - 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.
Patients do not receive therapeutic immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.


Other interventions: therapeutic immune globulin
Given IV

Other interventions: clinical observation
Undergo observation

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: prednisone
Given orally

Treatment: Surgery: magnetic resonance imaging
Correlative studies

Other interventions: laboratory biomarker analysis
Correlative studies

Treatment: Drugs: Corticotropin-Releasing Hormone
administered subcutaneously

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Changes from baseline to 2 months, 6 months, and 1 year
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Changes from baseline to the better of 6 months or 1 year
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Changes from baseline to the better of 6 months or 1 year
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
At diagnosis, 6 months, 1 year, 5 and 10 years after diagnosis
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
At diagnosis and yearly for 10 years after diagnosis
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Tumor Outcome in Terms of Overall Survival (OS) Rate - OS rate from time of study enrollment.
Timepoint [6] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
- 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

- 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

- Patients must be free of any organ dysfunction or disorder that the treating physician
feels may preclude the use of corticosteroid therapy (ACTH or prednisone),
cyclophosphamide therapy or intravenous gammaglobulin therapy.
Minimum age
No limit
Maximum age
8 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
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Florida
Country [10] 0 0
United States of America
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Georgia
Country [11] 0 0
United States of America
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Idaho
Country [12] 0 0
United States of America
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Illinois
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United States of America
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Indiana
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Kentucky
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United States of America
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Louisiana
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United States of America
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Maryland
Country [17] 0 0
United States of America
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Massachusetts
Country [18] 0 0
United States of America
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Michigan
Country [19] 0 0
United States of America
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Mississippi
Country [20] 0 0
United States of America
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Missouri
Country [21] 0 0
United States of America
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Nevada
Country [22] 0 0
United States of America
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New Jersey
Country [23] 0 0
United States of America
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New York
Country [24] 0 0
United States of America
State/province [24] 0 0
North Carolina
Country [25] 0 0
United States of America
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Ohio
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Oklahoma
Country [27] 0 0
United States of America
State/province [27] 0 0
Oregon
Country [28] 0 0
United States of America
State/province [28] 0 0
Pennsylvania
Country [29] 0 0
United States of America
State/province [29] 0 0
South Carolina
Country [30] 0 0
United States of America
State/province [30] 0 0
South Dakota
Country [31] 0 0
United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Vermont
Country [34] 0 0
United States of America
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Washington
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United States of America
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West Virginia
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United States of America
State/province [36] 0 0
Wisconsin
Country [37] 0 0
Canada
State/province [37] 0 0
British Columbia
Country [38] 0 0
Canada
State/province [38] 0 0
Nova Scotia
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Canada
State/province [40] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 eye and trunk muscle movements (known as opsoclonus myoclonus ataxia)
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.
Chemotherapy(cyclophosphamide), prednisone and intravenous gamma globulin all suppress the
immune system which may be helpful in treating opsoclonus-myoclonus-ataxia (OMA).
Trial website
https://clinicaltrials.gov/show/NCT00033293
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pedro De Alarcon, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications