Acalabrutinib and Durvalumab in Primary and Secondary Central Nervous System Lymphoma

Study Summary

BTK inhibition and checkpoint blockade are promising classes of therapy for central nervous system (CNS) lymphoma and have demonstrated efficacy with acceptable toxicity. A multidrug approach may carry a higher chance of durable efficacy in this aggressive disease that carries significant morbidity and mortality. Given the poor outcomes and limited options for patients who are not candidates for high-dose methotrexate, the investigators seek to evaluate the combination in this patient population. 08/30/2022: The study was originally designed for those with primary and secondary central nervous system (CNS) lymphoma. However, the first three patients who were enrolled all had secondary CNS lymphoma and most had germinal center phenotype disease with double hit phenotypes. In these three patients, two dose limiting toxicities were seen including 1 patient with grade 4 neutropenia at the time of disease progression and one with pneumonia in the setting of disease progression and worsening of existing heart disease. The third patient came off for clinical progression within cycle 1. Given the lack of response in patients with secondary CNS lymphomas, who do not exhibit the same biology as primary CNS lymphoma patients, Amendment 3 updates the study to only include patients with primary CNS lymphomas.

Primary Outcome

* Defined as Dose Level 2 if 0 or 1 dose limiting toxicities (DLTs) are seen in patients at that dose level, or Dose Level 1 if 2+ DLTs are seen in Dose Level 2 but only 0 or 1 DLTs are seen in patients at Dose Level 1. * A DLT is defined as the occurrence of an adverse event (AE) that is at least possibly related to the investigational product (IP) or investigational regimen (IR)

Conditions Studied

Interventions

• DRUG Acalabrutinib
• DRUG Durvalumab

Study Locations (2)