Trial to test acalabrutinib for patients with blood cancer, COVID-19
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The increasing number of deaths in the United States due to COVID-19 has underscored the need to identify populations at elevated risk for virus-related mortality.
These include patients with blood cancer, whom studies showed have a 30% to 60% higher risk for death due to COVID-19 infection than their cancer-free counterparts, according to The Leukemia & Lymphoma Society (LLS).
In response to this heightened mortality risk, the society has partnered with AstraZeneca to launch the first clinical trial designed to evaluate treatment for these patients, who often are excluded from COVID-19 trials due to low blood counts.
The BEAT COVID trial will be led by Michael Boyiadzis, MD, director of the clinical and translational research program at University of Pittsburgh, and will be modeled partly after LLS’s BEAT AML Master Clinical Trial, launched in 2016 at 16 cancer centers to test several drugs for patients with acute myeloid leukemia.
“We’re using the infrastructure that we’ve created within BEAT AML,” Amy Burd, PhD, vice president of research strategy for LLS, told Healio. “We’re using all the same clinical sites, which allows us to rapidly get the trial up and running so that we can enroll patients quickly. We’re using many of the same technologies and essentially the whole platform of BEAT AML. It shows we are able to rapidly pivot and use this same platform to study other diseases.”
Patients enrolled in BEAT COVID will receive the Bruton tyrosine kinase inhibitor acalabrutinib (Calquence, AstraZeneca), which is approved in the United States for treatment of chronic lymphocytic leukemia and relapsed or refractory mantle cell lymphoma and in anecdotal accounts has demonstrated potential to mitigate COVID-19 effects.
Healio spoke with Burd and John C. Byrd, MD, a HemOnc Today Editorial Board Member and distinguished university professor at The Ohio State University, and the chief medical officer for the BEAT AML trial.
Question: What additional risks do patients with blood cancer face when infected with COVID-19?
Byrd: As the pandemic hit, we feared patients with blood cancer would be at increased risk because of their compromised immune systems and low blood counts. That is exactly what occurred. In England, the largest study of patients who developed COVID-19 showed those aged older than 70 years and those with blood cancer were at very high risk for death or serious COVID-19 complications. Similarly, a real-world analysis by investigators in the United States showed patients with CLL who developed COVID-19 that required hospitalization had an approximately 40% mortality rate due to the virus. There are also small reports from other groups showing this; it’s a recurring theme.
Q: What is acalabrutinib’s potential mechanism in treating this patient population?
Byrd: COVID-19 induces a very potent activation of the immune system that, in many patients, is uncontrolled. When you look at people who have died of COVID-19, you see that there are a lot of inflammatory cells and many similarities to people who get very serious influenza A infections. Because influenza A has been around for a long time, there has been research over the past decade on the target of the drug we are testing, which is Bruton tyrosine kinase (BTK). This research in mice by several groups has shown that when you delete or inhibit BTK with a BTK inhibitor, you can give them a lethal dose of pneumonia, or a lethal dose of influenza A that induces an uncontrolled immune response, and the BTK inhibitor will prevent the mice from dying and reverse the inflammation. So, this study is built upon the idea that acalabrutinib is going to decrease that inflammatory response that causes people infected with COVID-19 to develop respiratory failure and go on the ventilator. It will allow them to develop an immune response to clear the virus. That’s the backbone of the study’s rationale.
Q: Could this benefit patients with COVID-19 who don’t have cancer?
Byrd: This is being tested right now. However, our study was put forward because patients with blood cancers, particularly acute leukemia, myelodysplasia and aplastic anemia, are not eligible for those studies because of their low blood counts.
Q: Can you describe the study design?
Byrd: It is a small, randomized study that will include about 60 patients. Our study is different from many others in that participants will receive either standard of care or standard of care plus acalabrutinib. There’s no seat belt. Placebos select out people of color, because minorities are suspicious of trials that are done with placebos. Also, our study does not have limitations in terms of blood counts, so it does not exclude patients with low blood counts.
Q: This trial will use some of the same information-sharing approaches used in BEAT AML. Can you discuss some of these?
Burd: We use myClin, a communication hub that allows us to keep the sites informed on everything from changes in protocol and safety information to daily updates on the trial. It allows sites to communicate with each other, as well. We also use Protocol First/Clinical Pipe, which enables us to populate our clinical database directly from the electronic health record. This is a time-saving aspect of the trial.
Q. Do you think acalabrutinib might become widely used among patients with COVID-19 and blood cancers?
Byrd: There is good science behind our approach. It has worked preclinically in a disease very similar to COVID-19, and we have seen phenomenal results in mice. This research may not have moved forward had LLS not been involved. The exciting part for me is how a drug that affects CLL and lymphoma can potentially have an impact on the COVID-19 pandemic, which is affecting so many people around the world.
Burd: It certainly shows the impact of the research that is done early in blood cancers and how it can span well beyond the reach of blood cancers.
Q: The research community reacted very quickly to COVID-19. What is the status of the research?
Burd: This pandemic has caused the whole world of researchers to come together with the shared goal of tackling this problem. So, there’s a tremendous amount of sharing, not only by pharmaceutical companies of what they are learning from studies, but also by the academic researchers of what they are learning at their institutions. It is this type of sharing that has sped the development of vaccines and trials like this one.
Byrd: It’s science translating to things that impact patients that will get us through this. It’s all of us working together.
Reference:
For more information:
Amy Burd, PhD, can be reached at The Leukemia & Lymphoma Society, 3 International Drive, Ste. 200, Rye Brook, NY 10573; email: amy.burd@lls.org.
John C. Byrd, MD, can be reached at 460 W. 10th Ave., Columbus, OH 43210; email: john.byrd@osumc.edu.
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