Summary

Eligibility
for people ages up to 8 years (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

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).

Official Title

A Pilot Study Randomized Trial of Intravenous Gammaglobulin Therapy for Patients With Neuroblastoma Associated Opsoclonus-Myoclonus-Ataxia Syndrome Treated With Chemotherapy and Prednisone

Details

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. 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.

Keywords

Disseminated Neuroblastoma Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Regional Neuroblastoma Stage 4S Neuroblastoma Neuroblastoma Prednisone Cyclophosphamide Immunoglobulins Antibodies gamma-Globulins Immunoglobulins, Intravenous Rho(D) Immune Globulin Hormones Adrenocorticotropic Hormone Melanocyte-Stimulating Hormones Corticotropin-Releasing Hormone beta-Endorphin therapeutic immune globulin clinical observation magnetic resonance imaging laboratory biomarker analysis chemotherapy, immunoglobulin therapy

Eligibility

For people ages up to 8 years

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.

Locations

  • University of California San Francisco Medical Center-Parnassus
    San Francisco California 94143 United States
  • Kaiser Permanente-Oakland
    Oakland California 94611 United States
  • Children's Hospital Central California
    Madera California 93636-8762 United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto California 94304 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Oncology Group
Links
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
ID
NCT00033293
Phase
Phase 3 Neuroblastoma Research Study
Study Type
Interventional
Participants
At least 53 people participating
Last Updated