EVE-Treg + Low-Dose IL-2 for Graft-versus-Host Disease

(EVENT Trial)

This trial tests a new treatment combination for chronic graft-versus-host disease (cGVHD), a serious condition that can occur after a stem cell transplant. Researchers aim to determine if Ex vivo-Expanded Regulatory T cells (EVE-Treg, a type of cell therapy) combined with low-dose Interleukin 2 (IL-2) can benefit individuals whose cGVHD hasn't improved with steroids or low-dose IL-2 alone. Participants will receive one of three doses of EVE-Treg with daily IL-2. This trial may suit those who have undergone a stem cell transplant, are currently managing cGVHD unresponsive to other treatments, and can maintain stable medication doses. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

The trial requires that you do not add or remove any immunosuppressive medications for 4 weeks before joining. You also cannot use certain medications like methotrexate, azathioprine, or a combination of a calcineurin-inhibitor and sirolimus.

In a previous study, researchers examined the safety of treatments similar to EVE-Treg for conditions like graft-versus-host disease (GVHD). These studies have shown that treatments using regulatory T cells are generally well-tolerated, with few serious side effects reported by patients. However, like all treatments, some risks exist. For example, some patients might experience mild flu-like symptoms.

As a Phase 1 study, the primary focus is on safety. This phase marks the first step in testing new treatments in humans and usually involves only a small number of patients to assess safety and determine appropriate dosage. While detailed safety data is still being collected, similar treatments in other studies suggest a reasonable safety profile so far.

Unlike the standard treatments for graft-versus-host disease, which often include immunosuppressive drugs like corticosteroids, EVE-Treg therapy uses ex vivo-expanded regulatory T cells to modulate the immune system more precisely. Researchers are excited because this approach aims to enhance the body's own regulatory pathways, potentially reducing harmful immune responses without broadly suppressing the immune system. The addition of low-dose IL-2 is intended to support the survival and function of these regulatory T cells, offering a more targeted and sustainable treatment option. This novel mechanism could lead to fewer side effects and improved outcomes for patients.

Research has shown that Regulatory T cells (Tregs), a type of immune cell, can help reduce graft-versus-host disease (GVHD) after a transplant. Tregs calm the immune system, preventing it from attacking the body. Studies have found that administering Tregs to patients can prevent long-term GVHD and improve overall immune health. Specifically, one study showed that patients who received Tregs had a much higher survival rate without severe GVHD. Additionally, combining Tregs with Interleukin-2, a protein that promotes their growth, enhances their benefits. This trial will evaluate different dose levels of EVE-Treg treatment, which could effectively manage GVHD in patients unresponsive to other treatments.⁶⁷⁸⁹¹⁰