Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)

Study Overview
=================
Brief Summary
-----------------
The OMS/DES study is a multinational European Trial for Children with the Opsoclonus Myoclonus Syndrome / Dancing Eye Syndrome. This trial brought on the way by specialists of the EPNS (European Paediatric Neurology Society), the GPOH (Gesellschaft für Pädiatrische Hematologic und Oncologie) and the SIOPEN (SIOP (International Society Oncology Pediatric) Europe Neuroblastoma). This protocol will investigate an escalating treatment schedule starting with a corticosteroid standard treatment with dexamethasone pulses (first step), which is followed, if response has been inadequate after 3 months of treatment, by the addition of CP (second step) and, if still no sufficient improvement, by the replacement of CP by Rituximab (third step). Treatment intensification is decided on the basis of standardized scoring of OMS/DES severity.

Official Title
-----------------
Multinational European Trial for Children With the Opsoclonus Myoclonus Syndrome / Dancing Eye Syndrome

Conditions
-----------------
Opsoclonus Myoclonus Syndrome, Neuroblastoma

Intervention / Treatment
-----------------
* Drug: Dexamethasone acetate
* Drug: dexamethasone and cyclophosphamide
* Drug: dexamethasone and rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children with newly diagnosed OMS/DES either NB-pos or NB-neg. Three out of the following four components are necessary for the diagnosis of OMS/DES: Opsoclonus or ocular flutter (but not nystagmus) Ataxia and/or myoclonus Behavioural change and/or sleep disturbance Neuroblastoma The diagnosis of OMS/DES may be difficult in some patients. Opsoclonus, in particular, may be intermittent or late in onset. A video example will be available at www.dancingeyes.org.uk. If uncertain, please contact the national coordinator for support in interpreting clinical features. Age 6 months or over up to less than 8 years (< 8th birthday) The date of diagnosis of OMS/DES is the date on which a doctor confirms the condition to be OMS/DES. The date of symptom onset needs also to be documented. Treatment start with the standard corticosteroid treatment with dexamethasone pulses as proposed by the guidelines given in this trial protocol (see 11.10, page 71). In patients with presumed NB-neg OMS/DES, neuroblastoma must be excluded according the guidelines of this trial (see chapter 4.4.1.4, page 30, and appendix 11.9, page 70) Documented informed consent for treatment and enrolment in the trial by parents / legal representatives. Exclusion Criteria: •Patients with opsoclonus, myoclonus or ataxia caused by other identified disease (e.g. current active CNS infection, neurometabolic disorder or demyelination). An identified viral precursor is not an exclusion criterion. prior or parallel use of chemotherapy (other than required for treatment of the neuroblastoma) Corticoid steroid for OMS/DES or other reasons lasting 14 days or more immediately before treatment start according the standard treatment proposed (treatment with corticosteroids for less than 14 days will be allowed) contre-indication of use of one of the experimental study drug (cf Summary of Product Characteristics used in this study)

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dexamethasone Cyclophosphamide Rituximab<br> | Drug: Dexamethasone acetate<br>* First step: immunosuppressive treatment with dexamethasone<br>Drug: dexamethasone and cyclophosphamide<br>* second step (in case of insufficient response): immunosuppressive treatment with dexamethasone and cyclophosphamide<br>Drug: dexamethasone and rituximab<br>* third step (in case of insufficient response): immunosuppressive treatment with dexamethasone and rituximab<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The response to treatment schedule as defined by the percentage of patients with disappearance of all symptoms. |  | at 48 weeks after treatment start |