In the treatment of children with acute myeloid leukemia “We have plateaued. The tools in our toolbox are all sledgehammers.”

This grim assessment was how Dr. E. Anders Kolb, of Nemours/Alfred I DuPont Hospital for Children, characterized the state of treatment for children with this devastating form of leukemia.

Dr. Kolb was among a group of pediatric oncologists to join The Leukemia & Lymphoma Society (LLS) in hosting an event in Atlanta in September to discuss LLS’s new $100 million Children’s Initiative, a multi-faceted effort to:

• double our investment in research;
• expand support services for patients and families;
• and launch a major collaborative clinical trial in acute leukemia

LLS is leading the charge to fundamentally change how we treat and care for children with blood cancer. But we can’t do it alone.  The audience for the Atlanta event was approximately 80 parents and advocates from foundations focused on children touched by blood cancer. They heard from a panel of doctors who have joined with LLS Chief Medical Officer Dr. Gwen Nichols to develop and implement a bold global LLS-led clinical trial to bring precision medicine to children with acute leukemia. The attendees participated in a spirited discussion about how they can get involved and help.

The need is urgent: While many children survive acute lymphoblastic leukemia, the most common type of pediatric blood cancer, the treatments are harsh and outdated. The long-term effects of current therapies can create severe life-threatening complications. And survival rates for children with other high-risk types of leukemia, such as acute myeloid leukemia (AML), are very poor.

Dr. Nichols and the doctors were joined by Michael Copley, who lost his daughter to AML, and Julie Guillot, who lost her son to AML, both of whom have volunteered to support LLS’s efforts.

Julie, who is volunteering as the chair of LLS’s Pediatric Partnerships and Outreach, showed a scene from the film, Dunkirk, as a metaphor for the collaboration needed to make the initiative a success. Just as thousands of civilian boats of all sizes sailed toward the shore of Dunkirk in France to rescue Allied troops trapped by the Germans during World War II, we’re all sailing in the same direction in our commitment to end childhood cancer. Whether you have a small sailboat, like the smaller foundations, or a cruise ship, like the larger nonprofits, everyone's contribution will be important and valued, she said. 

Julie, Dr. Nichols and the doctors, highlighted the obstacles that have historically prevented pharmaceutical companies from advancing no more than four therapies for first use in children over four decades. Childhood AML is biologically different from adult AML, so the drugs developed for adults don’t work well for these children. But the small patient population of children with the disease creates an unfavorable business model for the pharma industry.  And there are other regulatory hurdles to studying drugs first in children due to an abundance of concern about the risks of testing therapies in children. Most of the research in pediatric cancer is taking place in academia where “proof of principle” studies are published, but don’t lead to new drugs in the pipeline.

The LLS PedAL trial is still in the planning stages and will have many facets to it. The doctors are currently working out details with regulatory agencies in the US and abroad, and drafting the protocols for the study. Dr. Sam Volchenboum of University of Chicago is leading an effort to create a “Data Commons,” a platform where pediatric cancer data from multiple institutions will be compiled in one place and made available to researchers worldwide. This can help doctors potentially match their patients to novel targeted therapies based on their molecular mutations and other factors.  

Dr. Todd Cooper of Children’s Hospital of Seattle is drafting the trial protocol, Dr. Soheil Meshinchi of Fred Hutchinson Cancer Center is in charge of identifying the biomarkers that will be the targets for the novel agents to be tested in the trial, and Dr. Kimberly Stegmaier of Dana-Farber Cancer Center is leading the preclinical work.

LLS PedAL will be modeled on LLS’s successful Beat AML master clinical trial for adult AML patients. As with Beat AML, PedAL will involve multiple pharmaceutical companies, multiple study arms and will use genomics and other technology to stratify the children based on their subtypes of disease.

As Dr. Kolb said, we need to do better.

“We’ve gotten as much mileage as we can over the drugs we’ve repurposed for children that were built for adults.”