01/09/2019
An international clinical trial to improve outcomes for children and adolescents with high-risk relapsed acute lymphoblastic leukaemia (ALL) recently confirmed the first two Australian enrollees – a five-year-old boy and an eight-year old girl from Adelaide.

Known as the IntReALL-HR trial, it represents one of their only potential treatment options as up to 40 per cent of patients in this high-risk category will die from this disease.
 
The first phase of the clinical trial involves the use of a promising pharmaceutical agent called Bortezomib, which scientists hope will give these patients and their family more time together and lead to their cure.
 
One of these scientists is Associate Professor Tamas Revesz, who is leading the Australia and New Zealand contributions to the trial.
 
A paediatric oncologist at Adelaide’s Women’s and Children’s Hospital and the hospital’s former Head of Haematology-Oncology, Professor Revesz’s research into the biology and treatment of childhood leukaemia has been widely published.
 
With the help of funding from The Kids’ Cancer Project, he says the clinical trial can now pay for the Bortezomib and the data management of all patients who will be enrolled in the study.

“As Bortezomib is not a new drug and has been trialled in adults, the pharmaceutical company wouldn’t give it to us for free for this trial as it can be bought on the PBS for another indication,” Professor Revesz explained.

“Without this funding, we wouldn’t have access to it.”

Life-changing research

Working with children’s cancer centres in Australia, Japan and Europe, Professor Revesz is hoping to increase remission and molecular remission rates for children with high-risk relapsed ALL.
 
“Remission is traditionally defined as the disappearance of leukaemia cells under the microscope, which, in quantitative terms, is less than five per cent of the original cells,” Professor Revesz explained.
 
“Molecular remission means that the leukaemia is not detectable or there is less than one leukaemia cell among 10,000-100,000 normal bone marrow cells.”

“The challenge is that high-risk patients not only have a higher rate of leukaemia relapse, but they also unfortunately have a very poor prognosis,” he said.

The first phase of the study involves the induction of Bortezomib, followed by further blocks of chemotherapy.
 
Professor Revesz said there are also additional studies. One involves looking at the genetic alterations of the cells of patients at high risk of relapse.
 
“When we diagnose a relapse, we repeat a lot of the tests that were completed during the original diagnosis,” he said. 

“However, we can now concentrate even more on some of the genomic changes that show specific mutations that can be instrumental in causing the relapse.”

“We can identify potential targets in the leukaemia cell metabolism that can be targeted and treated at a later stage if necessary.”
 
Professor Revesz explained the trial’s second add-on study includes the use of a bispecific antibody that uses the patient’s own attack T-cells to destroy the leukaemia cells.

“After this, all patients will be eligible for bone marrow transplantation,” said Professor Revesz.

“Eventually, the results of all these study components will be analysed separately and together.”

Making a difference

Professor Revesz, who trained in Hungary, the UK and the US, said medicine seemed like a natural career choice as both his parents were doctors.
 
“When I did a paediatric module in my last years of medical school, I realised that I loved working with kids,” he said.

“I wanted to be involved in a sub specialty that was likely to develop quickly and, at the time, most of the children with leukaemia didn’t live very long. I thought I could make a difference, and there were reports coming out of the US and the UK that suggested that developments were being made.”

“I’ve seen a lot of my colleagues burn out in this field because it can be very stressful,” he said.

“At the same time, when you realise the difference that you can make to these children, it keeps you going.”

Professor Revesz worked as a paediatric oncologist in the UAE for nine years before being invited to work in the Netherlands on bone marrow transplantations.

In 2004 he was invited to move to South Australia to become Head of Haematology-Oncology at the Women’s and Children’s Hospital, where he continues to work part-time today.

“It was a wonderful opportunity and I also had a little a push from my wife, who is originally from Adelaide,” he said.

The study into high-risk relapsed ALL reached clinical trial stage last year, however Professor Revesz said much was involved in such a trial before patients could be recruited.

“Clinical trials quite rightly require tonnes of paperwork,” he said. “Even though we reached trial stage last year, we only got approval to treat patients at the beginning of this year.”

“Our first patient is currently undergoing consolidation treatment and has received Bortezomib during Induction,” added Professor Revesz.

“He is currently recovering from an infection and we are hoping to transfer him to Sydney Children’s Hospital for the randomized third block (bispecific antibody vs ‘conventional’) chemotherapy and also for his stem cell transplantation.”

“It’s early days, but we have every hope that he will do well.”

The second patient is currently finishing induction treatment (the first in a series of therapeutic measures taken to treat a disease). She could not receive Bortezomib because there were some concerns that the eight-year-old might develop bleeding complications. However, her data will also be very important for evaluating the study.

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