NCT04462328

Acalabrutinib and Durvalumab in Primary and Secondary Central Nervous System Lymphoma

Phase I Study With Dose Expansion of Acalabrutinib and Durvalumab (MEDI 4736) in Primary and Secondary Central Nervous System Lymphoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Primary Central Nervous System Lymphoma

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab will be administered over 60 minutes
DRUG	Acalabrutinib	Patients will take acalabrutinib orally every 12 hours (+/- 3 hours) daily.

Timeline

• Start date: 2021-04-29
• Primary completion: 2026-08-31
• Completion: 2028-05-31
• First posted: 2020-07-08
• Last updated: 2026-03-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study