Poster Presentation Advances in Neuroblastoma Research Congress 2016

OMS/DES 2011 : a Multinational European Trial for Children with Opsoclonus Myoclonus Syndrome (#330)

Barbara Hero 1 , Mike Pike 2 , Lim Ming 3 , Kate Wheeler 2 , Kevin Rostasy 4 , Andrea Klein 5 , Ruth Ladenstein 6 , Ingrid Ora 7 , Maria Bermúdez Cortés 8 , Felix Niggli 9 , Massimo Conte 10 , Elisa de Grandis 10 , Anne Jochem 11 , Marc Tardieu 12 , Gudrun Schleiermacher 11
  1. University of Cologne, Cologne, Germany
  2. John Radcliffe Hospital, Oxford, United Kingdom
  3. King's College Hospital, London, United Kingdom
  4. Kinderklinik Datteln, Datteln, Germany
  5. Unversitätsklinikum Basel, Basel, Switzerland
  6. Children's Cancer Research Institute, Vienna, Austria
  7. University of Lund, Lund, Sweden
  8. Murcia Hospital, Murcia, Spain
  9. University Children's Hospital, Zürich, Switzerland
  10. I. Gaslini, Genoa, Italy
  11. Institut Curie, Paris, France
  12. Hôpital Bicetre, Le Kremlin-Bicêtre, France

Background : Opsoclonus myoclonus syndrome (OMS) is a rare paraneoplastic syndrome characterized by opsoclonus, myoclonus and ataxia, as well as behavioural abnormalities, and is frequently associated with neuroblastome (NB) in children. Although oncological outcome is often favorable, neurological outcome remains poor.

Methods: SIOPEN (SIOP Europe Neuroblastoma), GPOH (Gesellschaft für Pädiatrische Hämatologie und Onkologie), and EPNS (European Paediatric Neurology Society) have launched a collaborative trial, using an escalating 3-step therapeutic design based on neurological response using standardized neurological evaluations. Neurological and oncological outcomes will be determined

Treatment steps:

  1. dexamethasone (20 mg/m2 x 3 days), monthly bolus (x12 months);
  2. if no neurological improvement after 3 months: cyclophosphamide 750 mg/m2, monthly bolus (x 6 months);
  3. -if no neurological improvement after 3 months: rituximab 375 mg/m2 x2.

 

Results: Since opening April 2013, the trial has recruited 31 of 100 planned patients. Enrolment rate has increased progressively: 6 patients in 2013, 9 in 2014 and 16 in 2015 due to successive trial opening in participating countries (n=7 to date). For the first 25 patients for whom complete datasets are available, mean age at diagnosis was 24 months (range 6-59m). NB was evidenced in 15 children (60%), of whom 7 required chemotherapy as oncological treatment. The protocol indications for tissue banking and neurological treatment have been adhered to, and to date 12 SAEs and no SUSARS have been reported.

 

Conclusion: The final opening (after 15 years) of this collaborative academic international paediatric trial involving neurologists and oncologists highlights administrative difficulties encountered prior to launching such a study, compliant with the European Clinical Trial Directive 2001/20/EC. The current lengthy timelines for trial activation across Europe must be improved with the new Clinical Trial regulation, and it is hoped that implementation of the new clinical trial regulation will improve this situation in Europe. This trial presents a unique opportunity for collaborative research across borders and specialties including biological research on mechanisms involved in OMS and OMS-associated NB.