Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders — NACHO-COBI  

Neuro-Degenerative Disease Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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 specfic 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. ;

Related Conditions & MeSH terms

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

• NCT number: NCT04079179
• Study type: Interventional
• Source: Baylor College of Medicine
• Contact: Carl E Allen, MD, PhD
• Phone: 832-822-4242
• Email: ceallen@texaschildrens.org
• Status: Recruiting
• Phase: Phase 2
• Start date: April 19, 2021
• Completion date: December 2029