Daratumumab for Familial Cerebral Cavernous Malformations: A Single-Arm Safety and Efficacy Study (NCT07026604) | Clinical Trial Compass
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 range
18 Years
Sex
ALL
See this in plain English?
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…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Incidence of severe infusion-related reactions (IRRs)
Timeframe: Up to 2 month
2
Change in total lesion volume on MRI during treatment