The Leukemia & Lymphoma Society (LLS) announced today a collaboration with the National Cancer Institute (NCI) and the Children’s Oncology Group (COG) to launch a global precision medicine clinical trial for children with acute leukemia. The three organizations share a commitment to address the urgent need for new, more precise and more effective treatments for children with cancer.
The new study, called LLS PedAL (Pediatric Acute Leukemia), is a master clinical trial that will test simultaneously multiple targeted therapies for children who experience a relapse of their acute leukemia, experienced by approximately 40% of children with AML, and 20% of children with high-risk acute lymphoblastic leukemia. The study will take place at more than 200 sites worldwide that are part of the NCI-supported COG network of children’s hospitals, including those in the U.S., Australia, New Zealand, and Canada. The LLS PedAL team will also collaborate with other overseas partners in the UK and EU to implement the trial in those regions. Through these established clinical trial infrastructures, nearly every child in these regions who experiences a relapse of acute leukemia will have access to the trial.
“NCI is committed to using every opportunity to improve treatments and outcomes for children with cancer,” said Malcolm A. Smith, MD, PhD, associate branch chief for pediatric oncology for NCI, which is part of the National Institutes of Health. “We look forward to partnering with parents and family advocates, The Leukemia & Lymphoma Society, and COG on this critical global initiative.”
A Comprehensive Approach to Address a Pressing Need
LLS PedAL is a key component of The LLS Children’s Initiative, the Society’s $100 million multi-year endeavor to attack pediatric blood cancer from every direction: research grants to advance novel treatments for children, enhanced free education and support services for children and their families, and new policy and advocacy efforts. With its Beat AML Master Clinical Trial, LLS has a proven track record of leading a precision medicine trial for adults with acute myeloid leukemia (AML), testing multiple novel targeted therapies and using advanced technology to rapidly identify patients’ disease subtype based on specific biomarkers and match them with treatments best suited for their diagnosis. A similar model will be used in the LLS PedAL trial, which will match children whose acute leukemia has returned with targeted therapies.
“Over the past 30 years, we’ve been using a one-size-fits-all approach to treat children with AML that doesn’t work for many of these children and they need better options,” said Gwen Nichols, MD, LLS chief medical officer. “Future progress depends on tailoring treatment to the specific vulnerabilities of each child’s leukemia. Through the LLS Children’s Initiative and LLS PedAL we are setting out to revolutionize the discovery of more effective therapies for children with acute leukemias while at the same time minimizing harm to healthy cells in children’s developing bodies.”
As with any clinical trial, before the LLS PedAL trial can launch, LLS must secure approval from the U.S. Food and Drug Administration (FDA) to begin testing therapies in patients. LLS will be responsible for regulatory submissions to the FDA and will be the Investigational New Drug (IND) holder. LLS plans to submit its IND application to the FDA later this year.
A Unique Collaboration
The NCI Pediatric Central Institutional Review Board (CIRB) will review all protocols for all of the sites in the COG network before the trial begins, to ensure patients’ safety. Having this one centralized review board as opposed to each of the hundreds of sites using their own IRB, will significantly speed the process. The COG Data Safety Monitoring Committee will provide oversight once the trial is under way.
The Children’s Oncology Group is an NCI-funded national clinical trials network of more than 9,000 clinical experts in childhood cancer at approximately 200 leading U.S. children’s hospitals and sites worldwide. All COG sites in the U.S., Canada, Australia and New Zealand will be eligible to participate in the LLS PedAL trial.
E. Anders Kolb, MD, Nemours Center for Cancer and Blood Disorders, chair of the COG Myeloid Disease Committee, and LLS Pedal co-chair said, “Many targeted therapies have been approved to treat adults with acute leukemia over the past decade, but few have been sufficiently studied in children to demonstrate their benefit. This study will give us the opportunity to learn what new targeted therapies are effective for children with acute leukemias.”
No Child Left Behind
The LLS PedAL trial will launch with three novel therapies to treat children with relapsed acute leukemia, with plans to add additional treatments as they become available. The study will ensure that every child with relapsed AML and many with ALL will be screened to identify their disease subtype and matched to the most appropriate treatment. Some of these patients will participate in LLS PedAL substudies, while others will be referred to other treatments, including other open clinical trials based on discussions with their physicians.
Data Commons: Data Sharing with a Common Language
Another important aspect of LLS PedAL will be a technology platform to enable participating institutions to consolidate, share and analyze data about pediatric blood cancer patients using standardized terminology. The data will help doctors better understand how children will respond to novel therapies, and the underlying causes of resistance or relapse.
“Our goal is to break down the silos that prevent researchers from sharing data about pediatric cancer patients,” said Sam Volchenboum, MD, Ph.D, of the University of Chicago, who is leading the data commons effort for LLS PedAL. “We are consolidating pediatric cancer data from multiple institutions into a single data set with a uniform dictionary of terms.”