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)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroblastoma; Opsoclonus Myoclonus Syndrome
• Intervention / Treatment: Drug: Dexamethasone acetate; Drug: dexamethasone and cyclophosphamide; Drug: dexamethasone and rituximab

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • St. Anna Kinderkrebsforschung e.V. CHILDREN'S CANCER RESEARCH INSTITUTE
• France
  • Amiens, France, 80054
    • CHU Amiens
  • Angers, France, 49933
    • CHU Angers
  • Besancon, France, 25030
    • Hôpital Jean Minjoz
  • Bordeaux, France, 33076
    • Chr Pellegrin
  • Caen, France, 14033
    • CHU Caen
  • Clermont Ferrand, France, 63003
    • Chu D'Estaing
  • Dijon, France, 21079
    • CHU Dijon
  • Grenoble, France, 38045
    • Chu de Grenoble
  • Limoges, France, 87042
    • CHU de Limoges
  • Paris, France, 75005
    • Institut Curie
  • Poitiers, France, 86021
    • CHU De Poitiers
  • Reims, France, 51092
    • CHU de Reims
  • Saint-denis, France, 97400
    • CHU LA REUNION Site Félix Guyon
  • Saint-Étienne, France, 42055
    • CHU Saint Etienne
  • Tours, France, 37044
    • Chu Tours Hopital Clocheville
  • Vandoeuvre Les Nancy, France, 54500
    • Hopital Nancy Brabois
  • Villejuif, France, 94805
    • Institut de Cancerologie Gustave Roussy
  • LE Kremlin Bicetre
    • Le Kremlin-Bicêtre, LE Kremlin Bicetre, France, 94275
      • CHU de Bicêtre
  • LYON Cedex 08
    • Lyon, LYON Cedex 08, France, 69373
      • Centre Leon Berard
  • Lille Cedex
    • Lille, Lille Cedex, France, 59020
      • Centre Oscar Lambret
  • Marseille Cedex 5
    • Marseille, Marseille Cedex 5, France, 13385
      • Hopita D'Enfants de La Timone
  • Montpellier Cedex 4
    • Montpellier, Montpellier Cedex 4, France, 34295
      • Hopital Arnaud de Villeneuve
  • NICE Cedex 03
    • Nice, NICE Cedex 03, France, 06202
      • Chu de Nice Archet 2
  • Nantes Cedex01
    • Nantes, Nantes Cedex01, France, 44093
      • Chr de Nantes
  • Paris Cedex 12
    • Paris, Paris Cedex 12, France, 75571
      • Ch Trousseau
  • Rennes Cedex 02
    • Rennes, Rennes Cedex 02, France, 35056
      • Chu Hopital Sud
  • Rouen Cedex
    • Rouen, Rouen Cedex, France, 76031
      • CHU de Rouen
  • Strasbourg Cedex
    • Strasbourg, Strasbourg Cedex, France, 67098
      • CHU DE STRASBOURG HOPITAL Hautepierre
  • Toulouse Cedex 9
    • Toulouse, Toulouse Cedex 9, France, 31059
      • CHU Toulouse Hopital des Enfants
• Italy
  • Genova, Italy, 16148
    • G. Gaslini Institut
• Spain
  • El Palmar, Spain, 30120
    • The Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
• Sweden
  • Lund, Sweden, 22185
    • University Hospital Lund
• Switzerland
  • Bern, Switzerland, CH 3010
    • Universitätskinderklinik
  • Zurich, Switzerland, 8032
    • Kinderspital Zürich
• United Kingdom
  • Oxford, United Kingdom, 0X3 9DU
    • John Radcliffe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Gudrun SCHLEIERMACHER, MD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2013
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: May 27, 2013
• First Submitted That Met QC Criteria: May 30, 2013
• First Posted (Estimated): June 4, 2013

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Neurologic Manifestations; Disease; 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; Syndrome; Neuroblastoma; Ocular Motility Disorders; Myoclonus; Opsoclonus-Myoclonus Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Dexamethasone; Dexamethasone acetate; BB 1101; Cyclophosphamide; Rituximab
• Other Study ID Numbers: IC 2011-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• IPD Sharing Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: SAP