- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00202930
Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Opsoclonus-myoclonus ataxia syndrome (OMS) is a rare immune mediated paraneoplastic syndrome that occurs in approximately 2 to 3% of children with neuroblastoma. Children with neuroblastoma associated opsoclonus-myoclonus tend to have a favorable prognosis from the standpoint of the cure of their cancer. Unfortunately,approximately two-thirds of this subgroup of patients are left with long term sequellae of the syndrome, including residual symptoms of opsoclonus, myoclonus, ataxia, learning difficulties and disturbance of sleep and mood.
Multiple lines of evidence indicate an immune mechanism to this rare disorder. This includes occurence of OMS in the post-infectious state, aggressive lymphocytic infiltration of the tumor in children with OMS, and documented responses to therapries that act through suppression of the immune system.
The current study utilizes four weekly doses of anti-CD 20 antibody (rituximab) to treat children with refractory OMS. Refractory disease is defined as continued symptoms of OMS despite surgical resection of the tumor and a minimum of one month of steroid therapy.
All patients have baseline OMS evaluation and detailed neurocognitive testing with all studies being repeated at the completion of the four weekly infusions. OMS testing is repeated at Month 3. OMS testing and detailed neurocognitive testing is conducted at 6 months intervals until 2 years from the initial infusion.
The goal of the study is to utilize this novel therapy to improve long term neurologic and neurodevelopmental outcome in children with refratory neuroblastoma associated opsoclonus-myoclonus.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Pathologic confirmation of diagnosis of neuroblastoma Surgical resection of primary tumor Symptoms of OMS despite a minimum of one month of steroid therapy Must meet all laboratory criteria to demonstrate adequate organ function -
Exclusion Criteria:
Patients currently receiving systemic chemotherapy for treatment of neuroblastoma Patients with documented active infection Patients who are HIV, Hep B or Hep C positive Organ toxicity from any prior therapy or surgical intervention must be resolved prior to study entry
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Rituximab
Single Arm
|
4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of Using 4 Weekly Rituximab Infusions
Time Frame: 4 weeks
|
To evaluate the feasibility of using 4 weekly Rituximab infusions in the treatment of children with neuroblastoma associated opsoclonus-myoclonus syndrome (OMS).
The first infusion involved a slow up titration from an initial rate of 0.5 mg/kg/hour to a maximum of 400 mg/hour.
If well tolerated, the subsequent infusions were administered at a starting rate of 1 mg/kg/hour to a maximum of 100 mg/hour for the first hour.
In the absence of adverse reaction doses were escalated by 1 mg/kg/hour (maximum 100 mg increase per hour) every 30 minutes to a maximum rate of 400 mg/hour.
If hypersensitivity or infusion related events occurred, the infusion was temporarily interrupted and resumed at 50% of the previous rate if reaction resolves.
The number of participants for whom the study dosing was feasible is reported.
|
4 weeks
|
Toxicity of Rituximab
Time Frame: Individuals were followed for adverse events until day 270
|
The trial was to be terminated early for any grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death.
The number of participants who experienced these events [grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death] is reported.
|
Individuals were followed for adverse events until day 270
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
OMS Evaluation Scale of Motor-Performance
Time Frame: Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
|
OMS Evaluation Scale of Motor-Performance This scoring system utilizes a scale of 0 to 3, with 0 being unaffected by OMS, and 3 representing those with severe impairment.
OMS testing will be scored by two independent scorers who have special expertise in the evaluation and management of children with neurologic disorders.
The mean of these scores will be obtained, and a standard error of the mean reported.
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Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
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Human-anti-chimeric Antibody (HACA) Development
Time Frame: Baseline; 3, 6, 9 months post treatment
|
Blood samples to be evaluated for the occurrence of antibody formation and potential effect on pharmacokinetic profiles.
|
Baseline; 3, 6, 9 months post treatment
|
Peripheral B Cell Depletion
Time Frame: 2 years
|
B cell depletion was measured through analysis of serum IgG levels.
The number of participants who experienced B cell depletion is reported.
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jean M Tersak, M.D., Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Eye Diseases
- Neurologic Manifestations
- Neurodegenerative Diseases
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Dyskinesias
- Nervous System Neoplasms
- Cranial Nerve Diseases
- Paraneoplastic Syndromes, Nervous System
- Paraneoplastic Syndromes
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Ocular Motility Disorders
- Myoclonus
- Opsoclonus-Myoclonus Syndrome
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- IRB0405652
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
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National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
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