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

Sponsor
Beijing Tiantan Hospital
Study ID
NCT07026604
Phase
EARLY_PHASE1
Status
Not Yet Recruiting

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Conditions

  • Cavernous Malformation, Cerebral

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Daratumumab — DRUG
    Participants receive intravenous daratumumab (16 mg/kg weekly for 8 weeks), diluted in 1000 mL (first dose) or 500 mL (subsequent doses) of saline, with infusion rates escalated stepwise from 50 to 200 mL/h under vital sign monitoring. Premedication (antihistamines/analgesics) is administered 30 minutes prior to each infusion to mitigate reactions.

Study Details

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.

Key Dates

Start date
Jul 1, 2025
Status verified
Jun 2025
Primary completion
Jul 1, 2026
Completion
Nov 1, 2026

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: intervention
    Participants receive intravenous daratumumab (16 mg/kg weekly for 8 weeks), diluted in 1000 mL (first dose) or 500 mL (subsequent doses) of saline, with infusion rates escalated stepwise from 50 to 200 mL/h under vital sign monitoring. Premedication (antihistamines/analgesics) is administered 30 minutes prior to each infusion to mitigate reactions. Weekly laboratory tests (hematology, liver/kidney function) and post-treatment MRI (3-month follow-up) assess safety and efficacy.

Primary Outcome Measure

Incidence of severe infusion-related reactions (IRRs) [ Time Frame: Up to 2 month ]

Central Contacts