Research team reports results of phase 1b clinical trial of CMVPepVax; larger study underway
DUARTE, Calif. — Infections caused by cytomegalovirus, or CMV, are a leading cause of complications in patients who undergo stem cell transplants. Antiviral drugs may reduce the risk of CMV infection, but they also cause toxic side effects and increase the chances of opportunistic bacterial or fungal infections.
City of Hope researchers now report that an innovative vaccine that boosts cellular immunity against CMV is safe and effective in stem cell transplant recipients. The research team reported results of a phase 1b clinical trial, published December 23 in The Lancet Haematology, which has paved the way for a larger and more definitive phase 2 study to assess effectiveness. That study is currently recruiting 96 participants.
In the phase 1b trial, researchers enrolled 36 participants who were scheduled to receive stem cell transplants for conditions such as leukemia or lymphoma. Half the participants received the vaccine, known as CMVPepVax, at 28 and at 56 days after the transplant, while the rest remained on standard treatments.
When the researchers tracked patients’ responses to the vaccine, they found that vaccinated patients had higher levels of protective T cells against CMV, showed less CMV re-activation, and needed fewer antiviral drugs compared to the unvaccinated group. “For the most part, CMV-specific T cells effectively control the virus in healthy individuals,” said Corinna La Rosa, Ph.D., associate research professor at City of Hope and a first author on the study. “Our data suggest that the vaccine boosts this T cell response in transplant recipients to mimic the healthy immune system’s response to CMV.”
The vaccine caused no unanticipated side effects, and general complications were fewer in the vaccine group, according to City of Hope hematologist Ryotaro Nakamura, M.D., associate professor at City of Hope and also a first author on the work. “Overall, people who received the vaccine had more robust immune recovery than those in the observation group,” he said.
“In the future, the CMVPepVax vaccine may prove useful not only for patients receiving stem cell transplants, but also for recipients of solid organ transplants or other immunodeficiency diseases,” said Don J. Diamond, Ph.D., senior author of the paper and the chair of the Department of Experimental Therapeutics at City of Hope. “The vaccine could play a role anywhere CMV could crop up as a problem, though logically it’s most applicable to stem cell transplants.” CMVPepVax was developed in Diamond’s lab.
The researchers noticed another small but surprising difference between the two groups in the current study: Those who received the vaccine appeared to have a lower risk of leukemia relapse, and suffered less non-relapse related mortality.
“We didn’t anticipate this to happen,” Diamond said. “Yet we found this striking signal from the data, which told us that those in the vaccine arm of the trial were less likely to relapse of their disease and less likely to develop problems that would lead to non-relapse mortality.”
These preliminary results must be validated before any conclusions can be drawn, the researchers emphasized. Because the phase 1b trial was open-label and conducted in a small group of patients, it’s possible these protective effects may be incidental findings. At present, it’s also unclear how or why a CMV vaccine could confer protection against leukemia relapse.
Nonetheless, these data warrant further investigation, Diamond said. In the ongoing phase 2 trial – a larger, double-blind study – the researchers will analyze data to see if these benefits persist. That trial, conducted in collaboration with researchers at the University of Minnesota, will compare patient responses to CMVPepVax after stem cell transplants and compare them to a placebo group.
“We want to get confirmation to see whether lightning ‘strikes twice’ with these effects,” said Diamond. “The current phase 2 trial, funded by the National Cancer Institute, will tell us whether the protective effects are really valid. If they are, it would be quite exciting.”
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant numbers 5R01 CA-077544, 1R01-CA181045 and P30-CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a comprehensive cancer center, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the nation. City of Hope’s main hospital is located in Duarte, California, just northeast of Los Angeles, with clinics in Antelope Valley and South Pasadena. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.
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