90Y-labelled anti-CD66 ab in childhood high risk leukaemia
Research type
Research Study
Full title
90-Yttrium-labelled anti-CD66 monoclonal antibody as part of a reduced toxicity conditioning regimen prior to allogeneic haematopoietic stem cell transplantation: an open label, phase II study in children and adolescents with high risk leukaemia
IRAS ID
292779
Contact name
Robert Chiesa
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS Foundation Trust
Eudract number
2019-001625-27
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Children affected by high risk or relapsed/refractory leukaemia have a poor prognosis, with an increased risk of relapse. These patients generally need treatment intensification and a bone marrow transplantation (BMT). Nevertheless, with conventional treatent the risk of relapse after transplant remains high.
Therefore new strategies are needed to eradicate leukemic cells prior to BMT in those children who have high risk disease.
It is well documented that leukemic cells are sensitive to irradiation and higher doses of irradiation achieve better leukaemia control. Nevertheless increasing the dose of irradiation is associated with increased toxicity and mortality after transplant.
Radioimmunotherapy provides a way to deliver high dose irradiation to the bone marrow (where leukaemia resides), while sparing normal organs and tissues from its toxicity.
This can be achieved by linking a radioactive molecule (Yttrium90) to an antibody that, once infused in the blood, targets marrow/leukemic cells.
In our Phase 1 trial which concluded in 2019, 9 children affected by refractory or relapsed leukamia were enrolled at Great Ormond Street Hospital or UCLH. Participants received infusion of a tumour cell targeting antibody to deliver irradiation to the bone marrow and sites containing leukemic blasts prior to BMT. The aim of the Phase 1 study was to identify the dose limiting toxicity and maximum tolerated dose of targeted radiotherapy, and it was found that this treatment was well tolerated with minimal infusion-related side effects.
The current study will enrol a larger cohort of children (aged 0.5 – 18 years) who will receive 90Yttrium administered at an infused activity to target the optimal absorbed dose to the bone marrow. Patients will be treated at GOSH and UCLH and followed up for 12 months post-BMT to evaluate safety and efficacy of targeted radiotherapy with a reduced toxciity conditioning regimen prior to BMT.REC name
London - Hampstead Research Ethics Committee
REC reference
21/LO/0371
Date of REC Opinion
18 May 2021
REC opinion
Favourable Opinion