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

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Trial phase: 
Phase III
Recruitment status: 
Recruiting

RATIONALE: 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. PURPOSE: This randomized phase II trial is studying cyclophosphamide, prednisone, and immunoglobulin to see how well they work compared to cyclophsophamide and prednisone alone in treating patients with abnormal trunk muscle movements associated with neuroblastoma.

Background information
Trial ID: 
NCT00033293
Other unique IDs: 
CDR0000069271
COG-ANBL00P3
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

Detailed description: 

OBJECTIVES:

  • 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.
  • Determine whether immunosuppressive therapy with cyclophosphamide and prednisone is an effective backbone therapy for OMA upon which to build additional treatment for these patients.
  • Determine whether these regimens improve OMA syndrome in these patients.
  • Determine whether these regimens improve motor coordination in these patients.
  • Determine whether these regimens improve functional outcome in these patients.
  • Compare the event-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk group per protocol COG-ANBL00B1 (low risk vs intermediate risk on COG-A3961 vs high risk on COG-A3973).

  • 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 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 thereafter.

PROJECTED ACCRUAL: A total of 18-52 patients (9-26 per treatment arm) will be accrued for this study within 2-5.8 years.

Number to be enrolled: 
52 patients
Clinical information
Age groups: 
Child
Gender: 
Both
Eligibility criteria: 

DISEASE CHARACTERISTICS:

  • Newly diagnosed neuroblastoma with tumor-associated opsoclonus-myoclonus-ataxia syndrome
    • 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

PATIENT CHARACTERISTICS: Age:

  • 8 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

PRIOR CONCURRENT THERAPY: Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy
  • Concurrent chemotherapy allowed

Endocrine therapy:

  • No prior prednisone or corticotropin

Radiotherapy:

  • Not specified

Surgery:

  • Concurrent surgery allowed

Study design: 
Treatment
Randomized
Active Control
Interventions: 
Observation
therapeutic immune globulin
Study arms: 
No Intervention: 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.
Conditions treated: 
Neuroblastoma
Outcome measurements: 

Efficacy as measured by assessment of response of opsoclonus, gait, neural, stance, arm and hand function at baseline, 2 months, 6 months, and 1 year [ Designated as safety issue: No ]

Response as measured by assessment of opsoclonus, gait, neural, stance, arm and hand function at baseline, 2 months, 6 months, and 1 year [ Designated as safety issue: No ]

Motor coordination as assessed by neurological examination and Vineland Adaptive Behavior Scale at baseline, 1 and 5 years [ Designated as safety issue: No ]

Functional outcome as assessed by age-appropriate neuropsychological testing at baseline, 1 and 5 years [ Designated as safety issue: No ]

Long-term prognosis for neurologic recovery by neurological examination at baseline, 1 and 5 years [ Designated as safety issue: No ]

Tumor outcome in terms of event-free survival and overall survival at 1, 5, and 10 years [ Designated as safety issue: No ]

Funding
Funding types: 
NIH
NETWORK
Sponsor: 
National Cancer Institute (NCI)
Children's Oncology Group
Dates
Date the data was first received: 
Tue, 2002-04-09
Trial start date: 
Mon, 2004-03-01
Trial completion date: 
Wed, 1969-12-31
Trial last updated: 
Wed, 2009-05-20