Wilmot Science Moves out of the Lab into a Clinical Trial

Dec. 4, 2020
Laura Calvi, M.D. (Photo taken prior to the COVID-19 pandemic)

Laura Calvi, M.D., achieved what a lot of translational researchers only dream of: For years, she made important discoveries in the lab, but then she was able to turn the project into a clinical trial, where it has begun to benefit patients.

“It’s an amazing accomplishment to get this far,” says Calvi, a co-leader of Wilmot Cancer Institute’s Cancer Microenvironment research program.

Many researchers, of course, intend for their basic science to eventually help patients. But the process can get derailed during the years it takes to develop goals, run experiments, publish the results, and then design and fund clinical trials. Sometimes good ideas don’t pan out, or funding is lost, or the scientist gets pulled in other directions.

In this case, though, a strong team approach made it happen. Calvi emphasized that moving the laboratory project into the clinical trial required a close collaboration with many Wilmot clinician-scientists, including Jane Liesveld, M.D.; Jason Mendler, M.D., Ph.D.; Michael Becker, M.D.; Frank Akwaa, M.D.; and Melissa Loh, MBBCh.

“This project represents a huge success,” Calvi says. “To hand off a concept to a clinical team that can run a study — it’s really, really difficult, but we’ve done it.”

Wilmot has several homegrown translational research projects in the pipeline — for instance, a clinical trial for glioblastoma, a type of brain cancer, is on the horizon, based on years of collaborative work done by Nimish Mohile, M.D., and Mark Noble, Ph.D. But Calvi’s case represents the most recent win. She took a series of discoveries about blood-forming and bone-forming stem cells in the bone marrow and created an innovative treatment idea for myelodysplastic syndrome (MDS).

MDS is a type of blood cancer that morphs into leukemia in about one-third of patients. A disease of aging, it occurs when blood cells in the bone marrow are defective (dysplastic) and cannot make healthy blood. As a result, patients with MDS usually require frequent blood transfusions.

In her clinical trial, Calvi combined an osteoporosis drug called abaloparatide, which builds bone and can also expand healthy blood cells, with another drug, bevacizumab, which blocks a growth factor common in many cancers. The goal, Calvi says, was to improve the environment for healthy blood stem cells and crowd out budding cancer cells.

Bob Coombs, shown here at a visit in February, prior to COVID-19, is part of a clinical trial of a new treatment for myelodysplastic syndrome.

Bob Coombs, 71, of Penfield, was among the first to volunteer for this trial.

“I was fortunate that my disease was discovered before it got really bad,” Coombs says. “That put me in a good position to help medical science. I was eager to help. I was under no illusions that this could be a cure, but at least we’ll advance knowledge.”

Calvi’s interests have centered on understanding how all of the tissues and cells in the bone marrow microenvironment contribute to MDS and other blood cancers. This approach is different from that of other scientists across the U.S., who are more focused on the malignancy itself.

She believes that improving the health of the blood supply and the entire bone marrow environment is key to reducing the risk of worsening MDS and leukemia.

As it turned out, Coombs’ health improved considerably while he was taking the experimental two-drug combination. His need for blood transfusions dropped from every two weeks to every six weeks.

“To go six weeks without a transfusion was pretty awesome,” says the retired software engineer and former town justice in Prattsburgh, Steuben County. Coombs lived in a rural area an hour south of Rochester for most of his life but recently moved to the Rochester suburbs to be closer to his daughter.

So far, all patients in the clinical trial have tolerated the treatment well, Calvi says. The phase 1 study was designed to measure safety, but the team also collected bone marrow samples and is analyzing data on the medications’ effectiveness.

When the trial is complete and if the results are promising, Calvi and her team  will seek National Institutes of Health funding for a larger clinical study.

The project bolsters three of Wilmot’s major research strengths: blood cancer investigation and treatment, an expertise in cancer and aging, and a growing understanding of how best to serve a predominantly aging population in Rochester and the surrounding upstate New York region.

Coombs says he was honored to be able to help improve medicine through clinical research.

“We need to give,” he says. “The world is a better place for it.”

The Mangurian Fund provided the support to purchase the study drugs, which have already been approved by the U.S. Food and Drug Administration. Calvi also received early support from the University of Rochester Clinical and Translational Science Institute.