New clinical trial gives hope to children with aggressive blood cancer

A new clinical trial for children with an aggressive type of blood cancer, led by researchers at UCL and Great Ormond Street Hospital (GOSH), will run alongside an adult clinical trial for the first time, with the hope of developing more targeted and effective treatments.

Dr. Sara Ghorashian (UCL Great Ormond Street Institute for Child Health and GOSH) and her team will be running the FRACTALL clinical trial for young people with T-cell acute lymphoblastic leukemia (T-ALL), whose T-ALL relapses or is resistant to conventional treatments, including chemotherapy and bone marrow transplant.

There is currently no standard of care for these children, and long-term survival can be as low as 30%. However, the new study will open at both GOSH and UCLH, meaning that patients aged up to 18 will have the opportunity to be involved.

The pediatric clinical trial is also adopting a novel approach which will see it running alongside an adult's clinical trial (taking place at UCLH) for the first time, in the hope of creating a more efficient trial design.

Dr. Ghorashian said, "Too often, children wait unacceptable amounts of time to access new cancer treatment which could make all the difference. This study will pave the way for research to always include children and make it a matter of course that both pediatric and adult patients are incorporated within clinical trials at the same time.

"Our goal is to never have a situation where children are left behind and we hope that we can prove the benefit of this novel approach to influence a change in the regulatory environment in the future."

Dedicated research projects for children's cancers are rare, with pediatric clinical trials traditionally starting later than adults' and taking an average of six-and-a-half years longer to complete. As a result, only 12 anti-cancer medicines have been authorized for pediatric cancer specifically in the last 10 years, compared to 150 for adult cancers.

The phase 1 clinical trial will treat 12 children with relapsed T-ALL. It will be testing the effectiveness of a CAR T-cell therapy targeted at a specific protein called CCR9, that has been newly identified by researchers at UCL, led by Dr. Paul Maciocia (UCL Cancer Institute) and Professor Marc Mansour (UCL Great Ormond Street Institute of Child Health), to occur exclusively on cancerous T-cells.

Through the trial, Dr. Ghorashian and her team are hoping to develop a new treatment that is more effective and targeted than current options.

CAR T-cell therapy, which involves genetically modifying the body's immune cells to recognize and kill cancer cells, has already shown remarkable success in children with B-cell acute lymphoblastic leukemia.

However, this has proven difficult to replicate in T-ALL as the cells used for therapy are the same as the cells of origin for the leukemia. This means that the CAR T-cells end up targeting either each other or the healthy T-cells, weakening the immune system even further. But with the recent discovery of the CCR9 protein, there is now a promising, clearer target. This is because CCR9 is a rare marker that is present on T-ALL but not on most healthy T-cells.

Not only will this new trial design potentially result in significant cost and time-savings, it will help ensure that children and adults have access to targeted therapies at the same time on the NHS. This is a step change from traditional clinical trial methods where adults take part first, which can mean that children don't even get the opportunity to try these potential treatments—despite children and young people often tolerating CAR T-cell therapy more robustly than adults.

Dr. Aoife Regan, GOSH Charity's Director of Impact and Charitable Funding, said, "In line with our new cancer research strategy, we are really proud to be funding this important study which will hopefully not only provide a potential new treatment option for children with a particularly aggressive form of cancer, but also lay the foundations for a new, more efficient clinical trial design that would benefit even more seriously ill children in the future.

"At GOSH Charity, we strive to give seriously ill children the best chance and the best childhood possible and are currently in the midst of the most ambitious appeal in our history to help build a new Children's Cancer Centre at GOSH. This game-changing new facility will help enable pioneering research to take place to deliver new breakthrough therapies for children who desperately need them."

Provided by University College London