NCT04079179

Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders

A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Carl Allen · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.

Detailed description

Histiocytic disorders are diseases caused by misfunctioning or buildup of particular immune cells called histiocytes. Many histiocytic disorders (LCH, juvenile xanthogranuloma (JXG), Erdheim-Chester disease (ECD), and Rosai-Dorfman Disease (RDD)) arises from blood cells that receive incorrect growth signals. These incorrect signals are caused by changes in genes (mutations) that lead to tissue damage (lesions) which causes disease. Some patients with LCH can develop neurodegeneration (LCH-ND) which is damage to neurons that results in reduced brain function, from LCH cells that go to the brain and activate inflammation. LCH arises from blood cells that receive incorrect growth signals. These incorrect signals are caused by mutations (changes in genes). The LCH blood cells can create changes in the structure of almost any organ, and can cause damage to normal organ function. The purpose of this research study is to learn whether cobimetinib is safe and effective in subjects diagnosed with LCH, LCH-ND, RDD, JXG and ECD which may have a specific mutation called BRAF-V600E. In healthy cells, certain proteins (called BRAF and MEK) are thought to help control normal cell growth. BRAF-V600E is a specific change in a gene that may cause cancer cells to grow and spread by sending constant signals to the MEK protein. Cobimetinib is designed to attach to and block the activity of MEK.

Conditions

• Langerhan's Cell Histiocytosis
• Juvenile Xanthogranuloma
• Erdheim-Chester Disease
• Rosai Dorfman Disease
• Neuro-Degenerative Disease
• Histiocytic Sarcoma
• Histiocytic Disorders, Malignant

Interventions

Type	Name	Description
DRUG	Cobimetinib	Cobimetinib will be administered at a maximal dose of 60 mg daily for patients \<18 years old and a flat dose of 40 mg daily for patients ≥18 years for 21 days on, then 7 days off, in a 28-day treatment cycle for a total of 12 cycles (approximately 12 months).

Timeline

• Start date: 2021-04-19
• Primary completion: 2025-12-01
• Completion: 2029-12-01
• First posted: 2019-09-06
• Last updated: 2025-09-18

Locations

12 sites across 1 country: United States

Regulatory

• FDA-regulated drug study