By Erin Jester
Adding one drug to a chemotherapy regimen for children with acute lymphoblastic leukemia decreased risk of relapse by about two-thirds, according to a study designed in part by John Kairalla, Ph.D., the senior statistician on the clinical trial and research associate professor and associate program director of the Children’s Oncology Group Statistics and Data Center in the College of Public Health and Health Professions’ Department of Biostatistics.
Results were presented in an oral plenary session on Dec. 7 at the American Society of Hematology’s annual meeting and published the same day in the New England Journal of Medicine.
The trial’s findings represent the biggest breakthrough in childhood cancer treatment in decades, said Kairalla, who is also a member of the UF Health Cancer Center.
B-cell acute lymphoblastic leukemia is the most common childhood cancer. While it has a high overall cure rate, relapses of the disease remain a leading cause of death among children.
Cure rates have increased dramatically over the last half-century, but progress has slowed, and other recent trials haven’t showed much promise.
Blinatumomab was a newer drug in 2017, when the research team began planning for the phase III clinical trial.
“During the study planning process, other options were considered, and it wasn’t a definite slam dunk choice for an active intervention on our clinical trial, but it was a bold choice at the time that really paid off,” Kairalla said.
Although clinicians, nurses and pharmacists are on the frontline of treating patients, biostatisticians like Kairalla are the invisible backbone of every meaningful clinical trial.
Before beginning any trial, biostatisticians use a method called power analysis to determine the probability of finding an effect if it exists. This informs sample size, length of the trial, timing of interim analyses, the likelihood of finding a relationship between treatment and outcomes, and many other reference points that are essential to understanding whether a treatment is effective.
“The whole trial could be a waste of time, resources and patient risk if study planning is not done correctly,” he said. “It’s not selling us short to say that statisticians are integral to pretty much every level of the clinical trial world.”
Patients began enrolling in the trial, which was funded through the National Cancer Institute’s Cancer Therapy Evaluation Program, in July 2019.
The trial ended early, in July 2024, after data from the first pre-planned interim analysis showed the drug reduced the relapse rate from 12% in the control group to 4% in the test group – a better outcome than expected. After reviewing the data with the trial’s master statistician, Cindy Wang, M. Sc., Kairalla and his team rushed the information out to the Data and Safety Monitoring Committee and, within days, the study chairs.
Even before results were formally published in December, interest in blinatumomab began to pick up steam globally based on talk about the study. Kairalla said the regimen is now the ideal standard of care for children with leukemia all over the world.
Separate trials on infants and adults have shown positive initial results, as well.
“The fact that it could have that much effect when added to a mature therapy that hasn’t budged outcomes in a while…the ramifications are huge,” Kairalla said. “Moments like this are the dream motivations for clinicians and statisticians alike and clearly show the real and lasting returns on investment for quality publicly funded research.”