Daratumumab for Familial Cerebral Cavernous Malformations: A Single-Arm Safety and Efficacy Study

Cerebral cavernous malformation (CCM) is a common vascular abnormality of the brain, affecting 0.1%-0.5% of people. It often causes recurrent brain hemorrhages, epilepsy, and neurological impairments, with surgery being the main treatment. However, surgery carries high risks for patients with multiple lesions or lesions in critical areas, and no effective pharmacological treatment is available. CCM is linked to mutations in genes like CCM1, CCM2, CCM3, or MAP3K3, which activate the MEK5-ERK5-KLF2/4 pathway, disrupting endothelial function. Immune cell infiltration, particularly plasma cells with high CD38 expression, suggests a role for humoral immunity in CCM. Depleting B cells in mouse models reduced lesions and hemorrhages, but broad B cell depletion is risky. To find a safer treatment, researchers tested anti-CD38 monoclonal antibodies in mice, showing that targeting CD38 reduced CCM lesion formation. Given the success of CD38-targeted therapies like daratumumab in treating multiple myeloma, this study proposes evaluating daratumumab for CCM in a single-center trial with 10 adult patients to assess its safety and efficacy.

NCT Number	NCT07026604
Lead Sponsor	Beijing Tiantan Hospital
Conditions	Cavernous Malformation, Cerebral
Enrollment	10 participants
Start Date	2025-07-01
Primary Completion	2026-07-01 (estimated)
Study Completion	2026-11-01 (estimated)
Updated on ClinicalTrials.gov	2025-06-18