Clinical trial NCT00202930: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuroblastoma
Opsoclonus-myoclonus
Keywords: neuroblastoma
Opsoclonus-myoclonus
rituximab
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2005-09-20
Enrollment: 4
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

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Primary outcomes:
measure: Feasibility of Using 4 Weekly Rituximab Infusions
timeFrame: 4 weeks
measure: Toxicity of Rituximab
timeFrame: Individuals were followed for adverse events until day 270
Secondary outcomes:
measure: OMS Evaluation Scale of Motor-Performance
timeFrame: Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
measure: Human-anti-chimeric Antibody (HACA) Development
timeFrame: Baseline; 3, 6, 9 months post treatment
measure: Peripheral B Cell Depletion
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
name: Jean M Tersak, M.D.
role: PRINCIPAL_INVESTIGATOR
References: