Chemotherapy Combinations for Mantle Cell Lymphoma

This trial compares three chemotherapy combinations to determine which is most effective for people with newly diagnosed mantle cell lymphoma, a type of blood cancer. The treatments being tested include combinations of drugs such as bendamustine, rituximab, cytarabine, and acalabrutinib (Calquence), each targeting cancer cells in different ways. The study aims to assess whether these combinations are more effective than the standard treatment. It is suitable for those with untreated mantle cell lymphoma who are seeking new treatment options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to explore promising new therapies.

The trial requires that patients switch from proton pump inhibitors to an alternative drug before starting acalabrutinib. Additionally, patients must not take strong or moderate CYP3A inhibitors or inducers within 7 days before the first dose of the study drug. If you are on these medications, you may need to stop or switch them.

Earlier studies have shown that the combination of bendamustine and rituximab is effective for patients with mantle cell lymphoma, with mostly mild side effects. Research indicates that this combination is generally safe. Some patients experienced side effects, but they were usually manageable.

When acalabrutinib was added to bendamustine and rituximab, studies found it to be safe overall. Patients tolerated the three drugs well, with most side effects not being serious. However, some experienced side effects like low blood cell counts, which doctors closely monitored.

Adding cytarabine to the mix has also been studied. Initial findings suggest this combination remains safe, but it may increase the risk of side effects like low blood cell counts and infections. Doctors manage these risks with regular check-ups and supportive care.

Researchers are excited about these chemotherapy combinations for Mantle Cell Lymphoma because they offer unique approaches compared to standard treatments like R-CHOP or BR (bendamustine and rituximab). Arm A utilizes a combination of bendamustine, rituximab, and cytarabine, which may enhance treatment effectiveness by incorporating cytarabine, a drug known for its ability to disrupt the DNA replication of cancer cells. Arm B includes acalabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, alongside bendamustine, rituximab, and cytarabine, potentially offering a more targeted approach by interfering with cancer cell signaling. Arm C combines acalabrutinib with bendamustine and rituximab, aiming to improve outcomes by targeting the BTK pathway, which plays a crucial role in the survival of lymphoma cells. These combinations could offer more effective alternatives with potentially different side effect profiles, sparking hope for improved patient outcomes.

In this trial, participants will join different treatment arms to evaluate the effectiveness of various chemotherapy combinations for mantle cell lymphoma. One arm will study the combination of bendamustine, rituximab, and cytarabine, which previous studies showed led to a complete remission rate of 91%, meaning many patients showed no signs of cancer after treatment. Another arm will investigate adding acalabrutinib to bendamustine and rituximab, as research has shown this combination significantly improved the time patients lived without their cancer worsening. Acalabrutinib blocks proteins that help cancer cells grow. Early studies have demonstrated that combining these treatments is safe and effective, supporting further research in treating mantle cell lymphoma.¹³⁴⁶⁷