Loncastuximab + Roflumilast for B-Cell Lymphoma

This trial explores a new treatment for people with diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. The aim is to assess the safety, tolerability, and effectiveness of the treatment in stopping or shrinking the cancer. Participants will receive a combination of medications, including loncastuximab (an antibody-drug conjugate) and roflumilast (a phosphodiesterase-4 inhibitor), to monitor their response. The trial seeks individuals with untreated DLBCL who are at high risk of a poor outcome. 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 treatment.

The trial requires you to stop using certain medications, including specific antibiotics, antifungals, and other drugs like St. John's Wort. If you're taking any of these, you may need to stop them before joining the trial.

Previous studies have shown that loncastuximab is effective and generally safe for patients with hard-to-treat B-cell lymphoma. It has been especially well-tolerated by patients who have tried many other treatments. Roflumilast has been tested as a repurposed drug for B-cell cancers and found to be safe. It works by blocking a specific enzyme that might aid cancer cell growth.

Loncastuximab combined with Roflumilast is unique because it offers a targeted approach to treating B-cell lymphoma. Unlike the standard R-CHOP regimen, which broadly attacks cancer cells, Loncastuximab specifically targets CD19, a protein on the surface of B-cells, potentially leading to more precise cancer cell destruction. Additionally, Roflumilast, an oral medication typically used for respiratory conditions, may enhance the immune response and reduce inflammation, adding a new dimension to the treatment. Researchers are excited because this combination could improve outcomes with fewer side effects, offering a promising new option for patients with high-risk diffuse large B-cell lymphoma.

In this trial, participants with high-risk diffuse large B-cell lymphoma (DLBCL) will receive a combination of treatments. Research has shown that loncastuximab can effectively treat patients with relapsed or hard-to-treat DLBCL, with about 32% of patients who had already received many treatments responding well to it. Roflumilast, another medication included in this trial, has proven safe and helpful when used with other treatments for high-risk DLBCL. It has shown promise when combined with standard chemotherapy. Together, these treatments aim to improve outcomes for patients with high-risk DLBCL by potentially increasing the response to treatment and slowing the disease's progression.³⁶⁷⁸⁹