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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemothera

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).

Detailed Summary:

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 if 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. Patie
Sponsor: Children's Oncology Group

Current Primary Outcome: Number of Responders [ Time Frame: Changes from baseline to 2 months, 6 months, and 1 year ]

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.


Original Primary Outcome:

Current Secondary Outcome:

  • Motor Coordination as Assessed by Neurological Examination and Vineland Adaptive Behavior Scale (VABS) [ Time Frame: Changes from baseline to the better of 6 months or 1 year ]
    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.
  • Functional Outcome as Assessed by Age-appropriate Neuropsychological Testing [ Time Frame: Changes from baseline to the better of 6 months or 1 year ]
    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.
  • 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 ]
    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 ]
    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: Up to 3 years ]
    EFS rate for neuroblastoma event from time of study enrollment.
  • Tumor Outcome in Terms of Overall Survival (OS) Rate [ Time Frame: Up to 3 years ]
    OS rate from time of study enrollment.


Original Secondary Outcome:

Information By: Children's Oncology Group

Dates:
Date Received: April 9, 2002
Date Started: March 2004
Date Completion:
Last Updated: April 18, 2017
Last Verified: June 2015