Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma
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| ClinicalTrials.gov Identifier: NCT00033293 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Results First Posted : October 3, 2016
Last Update Posted : April 18, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Regional Neuroblastoma Stage 4 Neuroblastoma Stage 4S Neuroblastoma | Other: Clinical Observation Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Procedure: Magnetic Resonance Imaging Drug: Prednisone Biological: Therapeutic Immune Globulin | Phase 3 |
PRIMARY OBJECTIVES:
I. 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.
II. Determine whether immunosuppressive therapy with cyclophosphamide and prednisone is an effective backbone therapy for OMA upon which to build additional treatment for these patients
SECONDARY OBJECTIVES:
I. Determine whether these regimens improve OMA syndrome in these patients. II. Determine whether these regimens improve motor coordination in these patients.
III. Determine these regimens improve functional outcome in these patients. IV. 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.
VI. Define better the long-term prognosis for neurologic recovery in the child with neuroblastoma associated with OMA syndrome. VII. Compare the event-free and overall survival of patients treated with these regimens.
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 53 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 15, 2004 |
| Actual Primary Completion Date : | December 10, 2013 |
| Actual Study Completion Date : | December 31, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (chemotherapy, immunoglobulin therapy)
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 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. |
Drug: Cyclophosphamide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Procedure: Magnetic Resonance Imaging Correlative studies
Other Names:
Drug: Prednisone Given orally
Other Names:
Biological: Therapeutic Immune Globulin Given IV
Other Names:
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Active Comparator: Arm II (chemotherapy, observation)
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 immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I. |
Other: Clinical Observation
Undergo observation
Other Name: observation Drug: Cyclophosphamide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Procedure: Magnetic Resonance Imaging Correlative studies
Other Names:
Drug: Prednisone Given orally
Other Names:
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- 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.
- 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.
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| Ages Eligible for Study: | up to 8 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- ≤ 0.4 mg/dL (for patients 1 to 5 months of age)
- ≤ 0.5 mg/dL (for patients 6 to 11 months of age)
- ≤ 0.6 mg/dL (for patients 1 year of age)
- ≤ 0.8 mg/dL (for patients 2 to 5 years of age)
- ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
- ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
- ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
- ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
- ≤ 1.6 mg/dL (for male patients ≥ 16 years of age)
- No prior IV gamma globulin therapy
- No prior chemotherapy
- Concurrent chemotherapy allowed
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No prior prednisone or corticotropin
- Patients who have received ≤ 14 days of steroids are eligible
- Concurrent surgery allowed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00033293
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| Principal Investigator: | Pedro A De Alarcon | Children's Oncology Group |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00033293 |
| Other Study ID Numbers: |
ANBL00P3 NCI-2009-00399 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-ANBL00P3 CDR0000069271 ANBL00P3 ( Other Identifier: Children's Oncology Group ) ANBL00P3 ( Other Identifier: CTEP ) U10CA013539 ( U.S. NIH Grant/Contract ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 27, 2003 Key Record Dates |
| Results First Posted: | October 3, 2016 |
| Last Update Posted: | April 18, 2023 |
| Last Verified: | January 2023 |
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Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Prednisone Cortisone Cyclophosphamide Immunoglobulins Immunoglobulins, Intravenous |
Antibodies gamma-Globulins Rho(D) Immune Globulin Immunoglobulin G Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Glucocorticoids |