Project Update - August 2024

This is specific to relapsed neuroblastoma - and the combination of AMXT 1501 and DFMO

Regarding the use of AMXT1501/DFMO (polyamine inhibition) therapy to treat cancer, the team leading the clinical trial in Australia has recently learnt of the possibility of developing severe cardiac toxicity resulting in cardiac arrest.

Consequently, a decision has been taken to pause development of its planned clinical trial of AMXT1501/DFMO in children with high-risk neuroblastoma and DIPG (diffuse intrinsic pontine glioma) until further information is available.

While AMXT1501/DFMO remains a potentially effective treatment approach, trialling this drug combination in children must be done safely and with all data to hand.

The Clinical Trial Team will therefore be carrying out extensive laboratory testing to explore a potential link between this drug combination and cardiac toxicity.

The Clinical TrialTeam is looking for any evidence of cardiac toxicity in their living models of disease and collaborating with cardiac experts to understand the mechanism of toxicity, and to investigate if any such toxicity can be avoided by changes in drugs, dosages or scheduling.

The Team is also awaiting the results of the AMXT1501/DFMO Phase 1 clinical trial currently underway in adult cancer patients. 

Research Project 

Professor Michelle Haber’s and Professor Murray Norris’s team at Children’s Cancer Institute discovered that a drug called DFMO was much more effective at killing neuroblastoma cells with the addition of a polyamine uptake inhibitor called AMXT 1501 (developed by Aminex Therapeutics). Should their promising pre-clinical research be successful, potentially new treatments can be developed for this devastating disease and improve survival rates for children with hard-to-treat relapsed neuroblastomas.

Exciting breakthrough with a combination drug therapy

Neuroblastoma Australia has agreed to support research into the drug DFMO conducted by Children’s Cancer Institute (CCI) . DFMO has been in clinical trial for a number of years and has shown it can affect neuroblastoma tumours.

The Team at CCI found that if DFMO were combined with a polyamine inhibitor, the drug becomes far more powerful in killing neuroblastoma cells. Polyamines are molecules which fuel the rapid growth of neuroblastoma cells.  As a result of their world-class research, a new trial testing this combination will be started in 2022. There is a strong rationale that this could ultimately lead to the development of potentially new treatments for this devastating disease and improve survival rates for children with hard-to-treat relapsed neuroblastomas.

As this research has shown such promising data to date, organisations in Europe and the US are also keen to support a clinical trial.