Ibrutinib + Chemotherapy for CNS Lymphoma

This trial explores a new treatment combination for primary central nervous system lymphoma (PCNSL), a rare and aggressive brain cancer. It combines the drug ibrutinib, which targets specific cancer cells, with a group of chemotherapy drugs (called TEDDI-R) to determine the safest and most effective dose. The trial focuses on patients whose PCNSL has returned or resisted previous treatments and who have had the condition confirmed through specific medical tests. Participants should be managing this challenging diagnosis and open to trying a different treatment approach. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

The trial does not specify if you must stop taking your current medications, but it does mention that you should not have taken certain treatments like chemotherapy or radiation therapy for at least 2 weeks before starting the trial. Additionally, you cannot use strong CYP3A inhibitors or inducers within 7 days before the trial.

Research has shown that the TEDDI-R treatment, which includes drugs like temozolomide, etoposide, doxil, dexamethasone, ibrutinib, and rituximab, is generally well-tolerated by patients. For instance, a study on a similar treatment called mini-TEDDI-R found that patients with CNS lymphoma experienced few serious side effects.

Evidence suggests that ibrutinib, a key component of TEDDI-R, has been tested in other CNS lymphoma studies and is usually considered safe. However, some patients might still experience side effects. In some studies, ibrutinib showed potential in treating CNS lymphoma, helping patients improve partially or completely.

Researchers are excited about the investigational treatments for CNS lymphoma because they incorporate ibrutinib, which offers a novel mechanism of action by targeting Bruton's tyrosine kinase (BTK). This approach is different from the standard chemotherapy and immunotherapy treatments like methotrexate and rituximab that are commonly used for CNS lymphoma. Ibrutinib's ability to inhibit BTK can potentially disrupt cancer cell survival pathways more effectively. Additionally, the trial explores combinations with drugs like isavuconazole, aiming to enhance treatment effectiveness and overcome resistance issues seen with existing therapies. This could mean more effective and rapid responses for patients battling this aggressive form of lymphoma.

Research shows that ibrutinib holds promise for treating central nervous system lymphoma, with studies indicating a 72% overall response rate, meaning many patients experience tumor shrinkage. In this trial, participants will receive different combinations of treatments. Some arms include Dexamethasone, which helps manage symptoms but doesn't significantly improve outcomes. Other arms involve Doxil, a type of doxorubicin, which doesn't reach the central nervous system well but still shows some effectiveness. Etoposide is included in certain arms and has successfully treated relapsed cases of this lymphoma. Rituximab, when combined with other treatments, improves response rates and survival chances. Temozolomide is also part of the study and has shown effectiveness in recurrent brain tumors, with some patients experiencing complete tumor disappearance. Together, these drugs aim to attack the cancer from different angles in the various treatment arms of this trial.⁶⁷⁸⁹¹⁰