Study Background

LCH is an inflammatory myeloid neoplasm with a wide spectrum of disease presentations. Outcomes for children with LCH remain poor with over half failing to be cured by initial therapy. Survival remains suboptimal in patients with high-risk disease (~85%), and over 70% of all patients have long-term consequences from disease and therapy.  There is no current standard of care for patients who fail initial vinblastine/prednisone chemotherapy and outcomes remain suboptimal. 

Approximately 10-25% of LCH lesions carry activating mutations in MAP2K1 (encoding MEK1).  In vitro studies support potential efficacy of targeted MEK inhibition in BRAF as well as MAP2K1 mutations. This study is designed to test the potential efficacy and toxicity of Cobimetinib, which targets MEK activation without paradoxical activation of the MAPK pathway in healthy cells.

Primary Objectives 

The primary objective of this study is to determine the overall response rates in children and young adults with recurrent active LCH lesions, in patients with LCH Neurodegenerative Disease (LCH-ND), in children and young adults with non-Langerhans cell histiocytic disorders, and in adults with histiocytic disorders to Cobimetinib. 

Secondary Objectives

  1. To estimate progression free survival in patients with histiocytic disorders with MAPK-activating mutations to Cobimetinib.
  2. To determine the nature and severity of adverse events in patients treated with Cobimetinib for histiocytic disorders.

Exploratory Objectives

  1. To evaluate response of histiocytic lesions with specific mutations (e.g. BRAF-V600E) to Cobimetinib.

Site Selection 

NACHO member centers were invited to complete and submit a NACHO-COBI Site Selection Questionnaire in 2019.
A limited number of centers have been selected to participate in the study during the initial site selection process.  Selected sites have been notified by the NACHO Operations Center. ​

Study Team

Clinical Coordinating Center
Texas Children's Hospital, Houston, TX USA

Operations & ​Data Coordinating Center
NACHO Operations Center housed at ​St. Jude Children's Research Hospital, Memphis TN USA

Study Chair
Carl E. Allen, MD, PhD
Texas Children’s Hospital, Houston, TN, USA

​Vice Chair
Olive S. Eckstein, MD
Texas Children’s Hospital, Houston, TN, USA

Study Manager 
Adrienne English, BSN, RN, CCRP
NACHO Operations Center

Project Coordinator 
Sara Hastings, CCRP 
NACHO Operations Center

ClinicalTrials.gov

View more information about this study on ClinicalTrials.gov Study NCT02639546.