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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

Study Primary Completion Date: June 2008

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.

Intervention(s) in this Clinical Trial

• Drug: therapeutic immune globulin
  • Given IV
• Procedure: observation
  • Patients do not receive immune globulin.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I (immune globulin therapy)
  • 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.
• No Intervention: Arm II (immune globulin therapy)
  • 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.

Primary Measures

• 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
  • 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
  • Safety Issue?: No

Secondary Measures

• Motor coordination as assessed by neurological examination and Vineland Adaptive Behavior Scale at baseline, 1 and 5 years
  • Safety Issue?: No
• Functional outcome as assessed by age-appropriate neuropsychological testing at baseline, 1 and 5 years
  • Safety Issue?: No
• Biology of neuroblastoma associated opsoclonus-myoclonus-ataxia syndrome, specifically by MRI findings, anti-neuronal antibodies, SCF findings and tumor biology at baseline, 6 months, and 1 year
  • Safety Issue?: No
• Long-term prognosis for neurologic recovery by neurological examination at baseline, 1 and 5 years
  • Safety Issue?: No
• Tumor outcome in terms of event-free survival and overall survival at 1, 5, and 10 years
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Newly diagnosed neuroblastoma with tumor-associated opsoclonus-myoclonus-ataxia syndrome
• Must enroll on study within 3 weeks of diagnosis
• Presence of opsoclonus, myoclonus, and/or ataxia associated with neuroblastoma considered eligible
• Currently enrolled on COG neuroblastoma protocols: COG-ANBL00B1, COG-A3961, or COG-A3973

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 8 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Oncology Group

Overall Clinical Trial Officials and Contacts

Pedro A. de Alarcon, MD Study Chair St. Jude Children's Research Hospital  

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00033293

Study ID Number: CDR0000069271

ClinicalTrials.gov Identifier: NCT00033293

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database