Cyclophosphamide + Bortezomib + Sitagliptin for Graft-versus-Host Disease

This trial explores a new combination of drugs—cyclophosphamide, bortezomib, and sitagliptin—to prevent graft-versus-host disease (GvHD), which can occur after a stem cell transplant. It targets adults with certain blood cancers receiving a transplant from a sibling or a closely matched donor. Those in remission but with at least one previous occurrence of their illness might be suitable candidates. The goal is to determine if these drugs can better protect patients from GvHD and enhance their recovery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

A previous study found that bortezomib was generally well-tolerated by patients. Some experienced side effects such as tiredness, nausea, and low blood platelets, but these were mostly mild to moderate. Cyclophosphamide, a chemotherapy drug often used in transplant settings, can cause side effects like hair loss and mouth sores, though these vary from person to person.

Sitagliptin, an FDA-approved drug for diabetes, is usually well-tolerated for that condition. Common side effects include headaches and a stuffy nose.

Most treatments for graft-versus-host disease (GVHD) typically involve immunosuppressive drugs like corticosteroids, but this investigational approach is different. Researchers are excited about the combination of cyclophosphamide, bortezomib, and sitagliptin because it targets GVHD with a unique three-pronged strategy. Cyclophosphamide is used after transplant to help control immune responses, bortezomib targets specific pathways in cells to reduce inflammation, and sitagliptin, commonly used for diabetes, is repurposed here to modulate immune activity. This combination offers a potentially more comprehensive and effective way to manage GVHD by addressing multiple aspects of the immune response simultaneously.

Research has shown that combining the drugs cyclophosphamide and bortezomib may help prevent graft-versus-host disease (GVHD) after stem cell transplants. In this trial, participants will receive varying doses of these drugs along with sitagliptin. Studies have found that using cyclophosphamide post-transplant results in a 73% chance of being free from chronic GVHD one year later. Additionally, sitagliptin is thought to reduce the risk of acute GVHD. This combination therapy has been linked to favorable survival rates; specifically, one study showed a 73% chance of survival one year after transplant, even with high-risk donors. These findings suggest that this treatment approach could effectively manage GVHD in transplant patients.⁶⁷⁸⁹¹⁰