Neuroblastoma has a high rate of relapse (over 50% in high-risk cases), and after relapse, fewer than 10% of children remain alive 5 years later. This therapy aims to improve the cure-rate of children with relapsed or refractory neuroblastoma by combining targeted radiotherapy (I-131 MIBG) with the antibodies anti-GD2 (ch14.18/CHO) and anti-PD1 (nivolumab). Laboratory studies have shown that this combination could be a powerful way of eradicating tumours and producing strong protective immunity and long-term cure.
Principal investigator: Dr Juliet Gray, University Hospital Southampton
Co-investigators: Dr Paul Sondel, University of Wisconsin, USA; Prof Holger Lode, University Medicine, Greifswald, Germany; Dr Mark Gaze, University College Hospital, London
Project partners: Solving Kids’ Cancer (US); J-A-C-K; Band of Parents
Total project award: $500,000
Our project grant: £96,000
Date of award: December 2015
Study Protocol: https://clinicaltrials.gov/ct2/show/NCT02914405
Neuroblastoma is an aggressive paediatric cancer that primarily affects children under 5 years old. For high risk cases, survival rates sit at 40-50%, dropping to 10% after relapse. There are no standard treatments available in the UK after relapse, meaning families must instead look to clinical trials for additional therapy options. Those abroad are not NHS funded and thus, are extremely expensive.
This trial is a collaborative project between organisations in both Europe and the USA, and is equally available to EU and US citizens. Founded on promising recent studies with a strong scientific rationale, it hopes to provide an innovative new treatment for relapsed and refractory neuroblastoma. If successful, this therapy would be available on an outpatient basis from centres in the UK, USA and Germany.
What difference will this project make?
A successful trial would result in a ground-breaking new therapy becoming available across international boundaries. Currently UK children facing relapse have no choice but to seek experimental clinical trials, of which many take place abroad and are not funded by the NHS. Families who choose to pursue therapies abroad face enormous hardships financially and emotionally, often turning to fundraising through public appeals. This charity-initiated clinical trial brings a new option to children in the UK on the NHS. Furthermore, this treatment would be less toxic than most current alternatives, with a low-treatment burden on children, and their families.
Here is a clip of Dr Juliet Gray talking about the trial at our 2016 Neuroblastoma Parent Education Conference.
What makes this project standout?
This trial arose from extensive international cooperation between charities and researchers to address an unmet need for novel approaches using immunotherapy for children with relapsed and refractory neuroblastoma. It is also the first to combine two antibodies and targeted radiation in one treatment; is less toxic than alternatives; and could have a drastic impact on the future of standard therapy.
About the research team
Dr Juliet Gray, MD is Senior Lecturer in Paediatric Oncology within Medicine at University Hospital Southampton, UK. She graduated from Cambridge University and the Royal Free Hospital, completed her clinical training in Paediatric Oncology at Southampton, Great Ormond Street, and the Royal Marsden hospitals, and completed her PhD in cancer immunotherapy within the Cancer Sciences Unit, University of Southampton. Dr Gray is a member of the NCRI Children’s Cancer and Leukaemia CSG Neuroblastoma Subgroup, the SIOP European Neuroblastoma Research Network and the UK Children’s Cancer and Leukaemia Group (CCLG) New Agents Group. She is the CCLG Clinical Trial Lead for the Southampton Paediatric Oncology Principal Treatment Centre, Chair of the Southampton Paediatric Chemotherapy Group.
Dr Paul Sondel, MD, PhD is Reed and Carolee Walker Professor in Pediatric Oncology at the University of Wisconsin, Madison. He completed both graduate and undergraduate education at UW-Madison and attained a PhD in genetics, before receiving his MD magna cum laude from Harvard Medical School. Dr Sondel has been a leader in scientific policy through multiple national committee roles, including The National Institutes of Health, The American Cancer Society, The Children’s Oncology Group (COG), The National Cancer Institute, where he was a member of the Board of Scientific Counselors, and St. Jude’s Children’s Research Hospital, where he was the Chair of their Scientific Advisory Committee and is now chair of their cancer center’s external advisory board.
Dr Holger Lode, MD is Professor and Chairman of Pediatrics and Pediatric Hematology and Oncology/BMT, and Director of the University Childrens Hospital in Greifswald. He studied at undergraduate level at Eberhard Karls Universität, Tübingen and Brown University, Providence, and received paediatric training at the University of Tübingen and the Charité University Medicine Berlin. Dr Lode is a member of the SIOP Scientific Programme Advisory Committee (SPAC) of the International Society for Pediatric Oncology Europe Neuroblastoma (SIOP), chair of the Immunotherapy Committee and member of the executive Board of SIOPEN.
Dr Mark Gaze, MD is consultant clinical oncologist at University College London Hospitals and Great Ormond Street Hospital for Children. He qualified from Saint Bartholomew’s Hospital and undertook specialist cancer training in Edinburgh and Glasgow. Dr Gaze is the lead for radiotherapy in clinical trials run by the European Paediatric Soft Tissue Sarcoma Group (EpSSG), and also for the International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN). He is Chairman of the Children’s Cancer and Leukaemia Group, is a member of the Specialist Training Board of the Faculty of Clinical Oncology, Royal College of Radiologists, and was formerly Chairman of the Specialty Training Committee in Clinical Oncology London, Kent, Surrey and Sussex and Eastern (Essex and Hertfordshire) Deaneries.
Our special thanks to Harvey, his parents Sarah and David and all of Harvey’s donors & fundraisers for helping to bring this clinical trial to fruition, continuing Harvey’s legacy.
“Harvey touched many people’s hearts and we can never express how grateful we are for all the support we received when fundraising for his treatment abroad. Sadly for us, this treatment was never to be but being able to use the funds for this new treatment, giving hope to other families, is a hugely positive step. Families having to raise funds, and travel across the world for treatment that could help their children beat neuroblastoma is an unacceptable situation to be in. Thanks to Solving Kids’ Cancer’s work and the generosity of the public in supporting Harvey’s Appeal, we’ve been able to bring this treatment to the UK so families won’t have to face this overwhelming situation. Neuroblastoma is difficult to treat and trials are few and far between but without vital funds for clinical trials, children will continue to be taken by this cruel disease and families will continue to be devastated.” Sarah and David Hext.