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Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00202930
Recruitment Status : Terminated (Closed early due to low accrual.)
First Posted : September 20, 2005
Results First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Jean M. Tersak, M.D., University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Opsoclonus-myoclonus Drug: anti-CD20 (Rituximab) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
Study Start Date : July 2005
Actual Primary Completion Date : December 2008
Actual Study Completion Date : February 5, 2009


Arm Intervention/treatment
Rituximab
Single Arm
Drug: anti-CD20 (Rituximab)
4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22
Other Name: Rituxan




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   2 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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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Information from the National Library of Medicine

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): NCT00202930


Sponsors and Collaborators
Jean M. Tersak, M.D.
Genentech, Inc.
Investigators
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Principal Investigator: Jean M Tersak, M.D. Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
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Responsible Party: Jean M. Tersak, M.D., Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00202930    
Other Study ID Numbers: IRB0405652
First Posted: September 20, 2005    Key Record Dates
Results First Posted: January 22, 2021
Last Update Posted: January 22, 2021
Last Verified: January 2021
Keywords provided by Jean M. Tersak, M.D., University of Pittsburgh:
neuroblastoma
Opsoclonus-myoclonus
rituximab
Additional relevant MeSH terms:
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Neuroblastoma
Opsoclonus-Myoclonus Syndrome
Myoclonus
Ocular Motility Disorders
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
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Central Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Paraneoplastic Syndromes
Neurodegenerative Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents