Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

NOT YET RECRUITING

NCT07026604

EARLY_PHASE1

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

Sponsor: Beijing Tiantan Hospital

View on ClinicalTrials.gov

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.

Official title: A Study on the Safety and Preliminary Efficacy of the Anti-CD38 Monoclonal Antibody Daratumumab in the Treatment of Refractory Familial Cerebral Cavernous Malformations

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-07-01

Completion Date

2026-11-01

Last Updated

2025-06-18

Healthy Volunteers

Conditions

Cavernous Malformation, Cerebral

Interventions

DRUG

Daratumumab

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.

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 controlled comorbidities, including chronic obstructive pulmonary disease (COPD), severe asthma, poorly controlled diabetes, renal and/or hepatic failure; * Cardiovascular diseases, including unstable angina, acute myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA Class II), arrhythmias requiring treatment (excluding premature beats or minor conduction abnormalities), deep vein thrombosis (excluding stable muscular vein thrombosis as judged by the investigator), pulmonary embolism, or other severe thromboembolic events, or history of deep vein thrombosis, pulmonary embolism, or severe thromboembolic events within 6 months prior to enrollment with a risk of recurrence as assessed by the investigator; * Participation in other interventional medical research or clinical trials within 4 weeks prior to screening (observational, natural history, or epidemiological studies without interventions are allowed); * Known allergic reactions to infused protein products; * Pregnancy (positive urine or serum pregnancy test in premenopausal women without documented surgical sterilization) or lactation; * Any condition (e.g., substance abuse, alcohol dependence) that, in the investigator's opinion, may compromise the participant's compliance with study requirements; * Participant or legal guardian unable to provide informed consent for the study.

Locations (1)

Beijing Tiantan Hospital

Beijing, China