PRA has partnered with The Leukemia and Lymphoma Society (LLS) on a global precision medicine clinical trial for children with relapsed acute leukemia, dubbed LLS PedAL.
PedAL is an extension of The LLS’s mission to cure leukemia, lymphoma, Hodgkin's disease, and myeloma. Through their work and research, they strive to improve the wellbeing of patients and their families.
Children with relapsed acute leukemia will be matched to treatments based on their unique leukemia biology. Multiple therapies will be tested simultaneously at approximately 200 clinical sites worldwide. The study data will be shared globally.
PedAL is composed of an impressive number of collaborators:
- Physicians, scientists, and regulators
- Parents, advocacy groups, and foundations
- Pharmaceutical companies
- A clinical research organization
This kind of collaboration will be an important consideration to the success of the pediatric oncology trials that will come as a result of the Research to Accelerate Cures and Equity (RACE) for Children Act.
To learn more about what this trial means for the future of pediatric oncology research and why it’s unprecedented for the industry, we spoke with experts from our Center for Pediatric Clinical Development, Business Development, and Project Management Project Delivery teams. Hear from the following experts below:
- Joanna Perkins, MD, MS, Medical Director, Hematology-Oncology
- Dawn Joseph, Account Director, Regional Sales
- Jacqui Whiteway, PhD, Pediatric Strategy Liaison, Scientific Affairs
- Missy Hansen, MSN, APRN, CNP-Pediatrics, Pediatric Strategy Liaison, Scientific Affairs
- Alice Teng, Project Director, Project Management Delivery
How did this partnership come about? Why is it unique?
JW: PRA’s philanthropy definitely contributed to the initial communication with the LLS surrounding this trial. Our team was asked to do a pediatrics capability presentation in Raleigh, NC. At the capabilities presentation, LLS started talking about PedAL’s master protocol.
DJ: We had an opportunity to communicate further about PedAL at an American Society of Hematology (ASH) conference. MDs from LLS talked about the organization’s desire to create a master trial and that they would be looking for CROs with extensive pediatric hematology and oncology experience. We continued to stay engaged with them and our team planned out what the study would look like. We were awarded the trial in September 2019.
PedAL is not an easy trial to run. It's a master trial consisting of multiple sub-studies, so we needed to get creative. We proved to the LLS that our approach was different. There was just great chemistry.
JP: This trial is unique because a CRO has never partnered with a nonprofit for a pediatric leukemia trial of this magnitude.
The LLS is running this master trial in collaboration with the Children's Oncology Group (COG). They’re the largest pediatric cancer consortium in North America, Australia, and New Zealand that oversees the majority of trials that are conducted in children with cancer.
Can you tell us more about the LLS and PRA’s PedAL partnership?
DJ: The collaboration between LLS and PRA is impressive. It will allow PRA to be a part of something tremendously important: bringing cures to kids with cancer. LLS initiated this trial prior to RACE, but with the RACE enactment just a month away, LLS is leading the way. PRA will demonstrate our strong pediatrics capabilities and our ability to manage and successfully run a complex master trial.
JP: It’s a pioneering collaboration—nothing like this has been done in pediatric cancer previously. It’s a master trial with many sub-studies planned.
This trial comes at a time when, because of the RACE for Children Act, all pharmaceutical companies previously granted exemptions from studying novel therapies in children will be required to have a pediatric research plan in place when launching an adult oncology trial. These pharmaceutical companies will search for CROs who are capable of assisting the companies with their research plans, especially in pediatrics.
Because of the magnitude of PedAL, all pharmaceutical companies that work in oncology will be aware of it.
MH: When the RACE for Children Act is enacted, all clinical oncology trials will need to comply. This will lead to many trials becoming master trials or complex trials. Master trials allow for fewer patients. PedAL is what is called an 'umbrella' trial, which means one indication (relapsed acute leukemias) but multiple drug targets. Patients may ultimately enroll in more than one sub-study.
With PedAL, we’re seeing collaboration between a multitude of drug sponsors, an advocacy group/nonprofit (LLS), a consortium, a CRO. This trial has banded together all of these agencies to hit on all aspects of the trial.
JW: Oncology has seen the greatest benefit from precision medicine over the past couple of decades because cancer is a molecular disease. As we’ve learned so much about cancer through the ‘omics revolution, from the ‘90s and the Human Genome Project on, oncology research has benefited the most from more targeted, precise medicine.
So far, this has benefited adults. RACE legislates that these advances are brought to children.
JP: Unfortunately, the majority of patients who are treated for childhood cancer will develop at least one chronic health condition later in life related to the conventional cytotoxic chemotherapies and/or radiation therapies they received. By dedicating more resources and increasing the number of clinical trials in precision medicine, the hope is that these more targeted molecular therapies will be associated with a much lower risk for long-term complications.
MH: In the face of the RACE Act, researchers will need to prioritize trials. Consideration will need to be given to what trials are presently available for each molecular target, what indications have been the most difficult with conventional therapies to improve overall survival, and what trials have difficult-to-manage short- and long-term effects.
What readily comes to mind is the relapsed/refractory diseases like the leukemias targeted in PedAL, as well as brain tumors. The side effects of the disease itself, surgeries, and therapies have significant impact on short- and long-term effects.
Equally important to prioritize are diseases like diffuse intrinsic pontine glioma (DIPG) of the brain, which is essentially incurable. It has an overall survival rate of less than 18 months. Following patients will be crucial in the precision medicine era. Researchers are optimistic that late effects may be minimized with more targeted therapies.
How is collaboration on a trial like PedAL going to lead to greater industry innovation?
JP: Working with such rare diseases requires a partnership to move forward and innovate. It requires collaboration. It requires an advocacy and fundraising organization like LLS, as well as the science behind the individual pharmaceutical companies and the products they develop.
We also can’t forget the people who manage all the nuts and bolts, making trials possible with CRO and COG partnerships. PedAL is going to set a precedent for many future studies to come by getting through all of the hurdles involved. One such hurdle is figuring out the budgeting for a study with 15+ sub-studies, all of which aren’t the same phase or size.
JW: With RACE, many sponsors are watching and waiting to see how PedAL will go. This will be the trial that all eyes are on. There are so many collaborative pieces up in the air, like the electronic Trial Master Files (ETMFs) and billing and budgeting when dealing with firewalled partners. With master trials, you must have a third party for the Investigational New Drug Application (IND), so that sort of complexity requires collaboration, too.
There's always the challenge of reaching age of consent or reassenting as kids inevitably age. I remember a challenge we discussed: these kids relapse. They go through the LLS screening trial, and if they relapse, there is a short period of time to match them up with a trial and a site.
In that short amount of time, the collaboration that will be required to match them to a site and a trial will be extraordinary, as well as ensuring they are appropriately informed and provide assent or consent. With 15+ trials, there’s a lot of information. You don't know which information will be going to which child and when. It will need to be done quickly and appropriately. Every child is critical.
AT: Collaboration leads to greater innovation. The LLS’s mission for this trial is to combine all these different partnerships together. It’s amazing to think about how all of us are coming together with this common goal of finding cures for individual patients.
How will PRA’s pediatric oncology expertise contribute to PedAL?
JP: Our expertise is the main reason why PRA was chosen. It’s unique for a CRO to have as many pediatric oncologists and operational staff with the required experience. It’s definitely unique to have the Center for Pediatric Clinical Development on board. This full-time staff dedicates 100% of their time to trials involving children.
A main focus of the team’s involvement with trials is to ensure that all aspects of trial participation are set up in the most conducive way for the child and family. The team ensures that the trial's end results are obtainable, ultimately retaining participation in trials, especially for pediatric oncology. Trials are an integral part of treatment discussions.
From a physician expertise standpoint, PRA has nine board-certified pediatric hematologists-oncologists on our staff. Our background is extensive—collectively, the North American pediatric hematologists-oncologists have over 100 years of clinical and research experience at 21 COG sites. PRA’s pediatric hematologists-oncologists, prior to coming to industry, have all had extensive experience on the front lines treating children with cancer. We’re strongly positioned to manage a trial like PedAL.
The RACE for Children Act: How Industry Can Accelerate Readiness Through Collaboration With Patient Organizations
This whitepaper offers a high-level orientation around the key barriers to readiness and critical success factors for companies navigating the…
Early Phase Innovative Pediatric Oncology Program Achieves Successful First Multiple Solid Tumors Study
PRA partnered with the sponsor’s new pediatric oncology department on an innovative pediatric oncology program. The program provided early evaluation…
Challenges Arise as the Need for Pediatric Research Increases
Many modern providers prescribe off-label treatment to children with “guesstimated” doses, because these drugs have often only been studied in…