Not Yet RecruitingEarly Phase 1

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

China10 participantsStarted 2025-07-01

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Age ≥ 18 years; * Diagnosed with familial cerebral cavernous malformation (familial CCM) (diagnosis requires at least one of the following: multiple CCMs or ≥2 family members with CCM); * Presence of clinical symptoms or history of symptomatic events: intracerebral hemorrhage, stroke, permanent or transient neurological deficits, seizures, disability, or any other neurological symptoms associated with cavernous malformations; * Deemed unsuitable for surgical resection by a physician; * Able to provide written informed consent; * Participant is willing and able to attend outpatient follow-up visits. Exclusion Criteria: * Stable familial CCM lesions not requiring intervention; * Presence of metal implants or other contraindications to MRI; * History of statin therapy within the past 6 months; * History of beta-blocker therapy within the past 6 months; * Laboratory abnormalities: absolute neutrophil count \<1 × 10⁹/L, platelet count \<100 × 10⁹/L, ALT \>2.5× upper limit of normal (ULN), ALP \>2.5× ULN, bilirubin \>1.5× ULN, serum creatinine \>2× ULN; * Known HIV positivity, hepatitis B virus seropositivity (excluding passive immunity from vaccination or immunoglobulin therapy), defined as HBsAg-positive and/or anti-HBs and anti-HBc positive, or known hepatitis C virus positivity; * Chronic or ongoing active infections requiring systemic treatment (e.g., chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis); * Poorly controll…

What they're measuring

Incidence of severe infusion-related reactions (IRRs)

Timeframe: Up to 2 month

Change in total lesion volume on MRI during treatment

Timeframe: Up to 2 month

Trial details

NCT IDNCT07026604

SponsorBeijing Tiantan Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-07-01

Contact for this trial

Yingfan Sun, Master of Clinical Medicine

+86 15140437077 yingfansun@hotmail.com