Overview

This trial is active, not recruiting.

Conditions disseminated neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma, stage 4s neuroblastoma
Treatments therapeutic immune globulin, clinical observation, cyclophosphamide, prednisone, magnetic resonance imaging, laboratory biomarker analysis, corticotropin-releasing hormone
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date March 2004
End date December 2014
Trial size 53 participants
Trial identifier NCT00033293, ANBL00P3, CDR0000069271, COG-ANBL00P3, NCI-2009-00399, U10CA013539, U10CA098543

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 trunk muscle movements 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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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 day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hr on day 0. Treatment repeats every 4 wks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 mths and then every other day for 7-15 mths. Patients receive therapeutic immune globulin IV on days -2 and -1, at wks 4, 8, 12, 16, 20, and 24, and then at mths 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. In case of progression of opsoclonus-myoclonus-ataxia (OMA) during evaluation, patient will be switched to another steroid, corticotropin-releasing hormone (ACTH).
therapeutic immune globulin BayGam
Given IV
cyclophosphamide CPM
Given IV
prednisone DeCortin
Given orally
magnetic resonance imaging MRI
Correlative studies
laboratory biomarker analysis
Correlative studies
corticotropin-releasing hormone ACTH
administered subcutaneously
(Active Comparator)
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. Patients do not receive therapeutic immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.
clinical observation observation
Undergo observation
cyclophosphamide CPM
Given IV
prednisone DeCortin
Given orally
magnetic resonance imaging MRI
Correlative studies
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
Motor coordination as assessed by neurological examination and Vineland Adaptive Behavior Scale (VABS)
time frame: Changes from baseline to 6 months or 1 year
Functional outcome as assessed by age-appropriate neuropsychological testing
time frame: At diagnosis and yearly for 10 years after diagnosis
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
Long-term prognosis for neurologic recovery by neurological examination
time frame: At diagnosis and yearly for 10 years after diagnosis
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
Tumor outcome in terms of overall survival rate
time frame: Assessed up to 10 years

Eligibility Criteria

Male or female participants up to 8 years old.

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.

Additional Information

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
Principal investigator Pedro De Alarcon, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.