Optimization of the Time and Dosage of Vemurafenib in BRAF Positive Juvenile Patients With Refractory Histiocytosis

What this Trial Is About

Researchers are evaluating the optimal timing and dosage of vemurafenib for juvenile patients with histiocytosis who have a BRAF gene mutation and whose disease is resistant to standard treatments. This Phase 2, open, randomized clinical trial is part of the POLHISTIO project aimed at improving diagnosis and treatment by analyzing gene mutations and their relationship to clinical outcomes. The study is designed to include patients aged 1 to 18 years from across Poland and focuses on improving event-free survival and molecular response measures. Participants receive vemurafenib at a dose of 20 mg/kg/day and are randomly assigned to one of two treatment durations: 6 months or 12 months after their BRAF mutation becomes undetectable. This targeted therapy is given following failure of conventional treatments, and the study compares outcomes depending on how long vemurafenib is continued after mutation negativization. The trial includes molecular testing of circulating tumor DNA to monitor mutation status and treatment response. During the study, participants will undergo regular monitoring including molecular tests to detect disease relapse, clinical assessments, and imaging such as MRI to check for neurodegenerative signs. Researchers will measure event-free survival over two years and track the time to negative mutation tests. The trial includes informed consent processes, adherence to contraception requirements where applicable, and ongoing evaluation of patient safety. Participation lasts throughout treatment and includes follow-up for at least two years to assess long-term outcomes.

Optimization of the Time and Dosage of Vemurafenib in BRAF Positive Juvenile Patients With Refractory Histiocytosis