Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
Primary Purpose
Neuroblastoma, Opsoclonus-myoclonus
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
anti-CD20 (Rituximab)
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring neuroblastoma, Opsoclonus-myoclonus, rituximab
Eligibility Criteria
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 -
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Rituximab
Arm Description
Single Arm
Outcomes
Primary Outcome Measures
Feasibility of Using 4 Weekly Rituximab Infusions
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.
Toxicity of Rituximab
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.
Secondary Outcome Measures
OMS Evaluation Scale of Motor-Performance
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.
Human-anti-chimeric Antibody (HACA) Development
Blood samples to be evaluated for the occurrence of antibody formation and potential effect on pharmacokinetic profiles.
Peripheral B Cell Depletion
B cell depletion was measured through analysis of serum IgG levels. The number of participants who experienced B cell depletion is reported.
Full Information
NCT ID
NCT00202930
First Posted
September 12, 2005
Last Updated
January 4, 2021
Sponsor
Jean M. Tersak, M.D.
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00202930
Brief Title
Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
Official Title
Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Closed early due to low accrual.
Study Start Date
July 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
February 5, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jean M. Tersak, M.D.
Collaborators
Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the feasibility of giving four weekly doses of Rituximab (anti-CD20 antibody) in the treatment of children with refractory neuroblastoma associated opsoclonus-myoclonus. Patients must have continued symptoms of opsoclonus, myoclonus and or ataxia despite surgical resection and a minimum of one month of steroid therapy. Evaluations include clinical symptoms of opsoclonus-myoclonus and ataxia as well as detailed evaluation of learning and development.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Opsoclonus-myoclonus
Keywords
neuroblastoma, Opsoclonus-myoclonus, rituximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Other
Arm Description
Single Arm
Intervention Type
Drug
Intervention Name(s)
anti-CD20 (Rituximab)
Other Intervention Name(s)
Rituxan
Intervention Description
4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22
Primary Outcome Measure Information:
Title
Feasibility of Using 4 Weekly Rituximab Infusions
Description
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.
Time Frame
4 weeks
Title
Toxicity of Rituximab
Description
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.
Time Frame
Individuals were followed for adverse events until day 270
Secondary Outcome Measure Information:
Title
OMS Evaluation Scale of Motor-Performance
Description
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.
Time Frame
Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
Title
Human-anti-chimeric Antibody (HACA) Development
Description
Blood samples to be evaluated for the occurrence of antibody formation and potential effect on pharmacokinetic profiles.
Time Frame
Baseline; 3, 6, 9 months post treatment
Title
Peripheral B Cell Depletion
Description
B cell depletion was measured through analysis of serum IgG levels. The number of participants who experienced B cell depletion is reported.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean M Tersak, M.D.
Organizational Affiliation
Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
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