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

• Response of opsoclonus-myoclonus-ataxia (OMA) to treatment as rated by stance, gait, arm and hand function, opsoclonus, and mood/behavior [ Time Frame: Changes from baseline to 2 months, 6 months, and 1 year ] [ Designated as safety issue: No ]
  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.
  
  

• Motor coordination as assessed by neurological examination and Vineland Adaptive Behavior Scale (VABS) [ Time Frame: Changes from baseline to 6 months or 1 year ] [ Designated as safety issue: No ]
  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 and compared using a one-sided t-test with a significance level of .05.
  
  
• Functional outcome as assessed by age-appropriate neuropsychological testing [ Time Frame: At diagnosis and yearly for 10 years after diagnosis ] [ Designated as safety issue: No ]
  Descriptive analyses of the scores from additional neurologic assessment tests will be performed.
  
  
• Biology of neuroblastoma associated opsoclonus-myoclonus-ataxia (OMA) syndrome specifically by MRI findings, anti-neuronal antibodies, cerebrospinal fluid (CSF) findings and tumor biology [ Time Frame: At diagnosis, 6 months, 1 year, 5 and 10 years after diagnosis ] [ Designated as safety issue: No ]
  Descriptive analyses on biologic variables will be performed
  
  
• Long-term prognosis for neurologic recovery by neurological examination [ Time Frame: At diagnosis and yearly for 10 years after diagnosis ] [ Designated as safety issue: No ]
  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.
  
  
• Tumor outcome in terms of event-free survival (EFS) rate defined as a relapse or progression of neuroblastoma, a second malignancy, or death [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
  The EFS and S rates will be calculated.
  
  
• Tumor outcome in terms of overall survival rate [ Time Frame: Assessed up to 10 years ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. Determine if immunosuppressive therapy with cyclophosphamide and prednisone is an effective therapy for neuroblastoma associated opsoclonus-myoclonus-ataxia (OMA) and can constitute a back-bone therapy upon which to build additional therapy.

II. Determine in a randomized study if the addition of intravenous gammaglobulin therapy to the back-bone therapy of prednisone and cyclophosphamide improves response of neuroblastoma associated OMA.

SECONDARY OBJECTIVES:

I. Determine if intravenous gammaglobulin therapy improves the motor coordination of children diagnosed with neuroblastoma and presenting with OMA syndrome as assessed by neurological examination and the Vineland Adaptive Behavior Scale (VABS).

II. Determine these regimens improve functional outcome in these patients. III. 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.

IV. Define better the long-term prognosis for neurologic recovery in the child with neuroblastoma associated with OMA syndrome.

V. Define the event-free and overall survival of patients with neuroblastoma associated opsoclonus-myoclonus-ataxia syndrome.

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.