Texas Children's Cancer and Hematology Center Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO COBI)


This is a Phase 2 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. Children with LCH that was not cured with initial chemotherapies, children with other histiocytocytic disorders who may or may not have received prior therapy, children and adults with LCH-associated neurodegeneration, and adults with histiocytic disorders will be treated on this study. This study was initiated by investigators at the TXCH Histiocytosis Program and is being operated and opened at multiple sites across the country through the North American Consortium for Histiocytosis (NACHO).


Histiocytic disorders are diseases caused by misfunctioning or buildup of particular immune cells called histiocytes. Histiocytic disorders (LCH, juvenile xanthogranuloma (JXG), Erdheim-Chester disease (ECD), and Rosai-Dorfman Disease (RDD)) arise from blood cells that receive incorrect growth signals. These incorrect signals are caused by changes in genes (mutations) that lead to develop of lesions that can damage normal tissue. Some patients with LCH can develop neurodegeneration (LCH-ND) where activated LCH cells in the brain cause damage to neurons that results in reduced brain 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. In almost all cases of these histiocytic disders, BRAF, MEK or other proteins in the MAPK cell growth pathway do not function correctly. Cobimetinib is designed to block the activity of MEK which is overactive in cells in histiocytic lesions.

Eligibility Criteria

  • Ages Eligible for Study: Children, Adult
  • Sexes Eligible for Study: All
  • Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
  • Biopsy proven LCH -AND
  • Failure of at least front-line therapy for high-risk LCH with evaluable disease. -OR
  • Failure of at least second-line therapy for low-risk LCH with evaluable disease. -OR
  • Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
  • Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease.

Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov.