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.
Overview
- Phase
- Phase 2
- Intervention
- Cobimetinib
- Conditions
- Langerhan's Cell Histiocytosis
- Sponsor
- Carl Allen
- Enrollment
- 90
- Locations
- 12
- Primary Endpoint
- Overall Response Rates using modified RECiST criteria
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief 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.
Investigators
Carl Allen
Associate Professor
Baylor College of Medicine
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Patients < 21 years with recurrent LCH (Grp1)
Children (≥ 6 months) and young adults (\<21 years) with recurrent active LCH lesions (may also have LCH-ND).
Intervention: Cobimetinib
Patients of any age with LCH-ND (Grp2)
Patients of any age (≥ 6 months) with progressive LCH Neurodegenerative Disease (LCH-ND) without other sites of active LCH.
Intervention: Cobimetinib
Patients <21 years with other histiocytic disorders (Grp3)
Newly diagnosed or relapsed/refractory children (≥ 6 months) and young adults (\<21 years) with other histiocytic disorders including juvenile xanthogranuloma, Erdheim-Chester disease, histiocytic sarcoma and Rosai-Dorfman disease.
Intervention: Cobimetinib
Patients ≥ 21 years with LCH/histiocytic disorders (Grp4)
Adults (≥21 years) with LCH or other histiocytic disorder with recurrent active lesions (may also have LCH-ND).
Intervention: Cobimetinib
Outcomes
Primary Outcomes
Overall Response Rates using modified RECiST criteria
Time Frame: 12 months
Proportion of participants with (complete response, partial response, stable disease, progressive disease) by 1 year of therapy with Cobimetinib. It is assumed that at each protocol-specified timepoint, a response assessment occurs. Status calculation will occur at each timepoint for patients who have measurable disease at baseline per the criteria defined in the protocol.
Secondary Outcomes
- Progression Free Survival(12 months)
- Nature and Severity of Adverse Events(12 months)