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

Phase 2

Recruiting

• Conditions: Histiocytic Sarcoma; Histiocytic Disorders, Malignant; Juvenile Xanthogranuloma; Langerhan's Cell Histiocytosis; Rosai Dorfman Disease; Erdheim-Chester Disease; Neuro-Degenerative Disease
• Interventions: Drug: Cobimetinib

• Registration Number: NCT04079179
• Lead Sponsor: Carl Allen

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.

Study Timeline

• Study First Submitted: 2019-08-10
• Study First Submitted QC: 2019-09-04
• Study First Posted: 2019-09-06
• Study Start: 2021-04-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-26
• Last Update Posted: 2024-08-28
• Primary Completion: 2024-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients < 21 years with recurrent LCH (Grp1)	Cobimetinib	Children (≥ 6 months) and young adults (\<21 years) with recurrent active LCH lesions (may also have LCH-ND).
Patients of any age with LCH-ND (Grp2)	Cobimetinib	Patients of any age (≥ 6 months) with progressive LCH Neurodegenerative Disease (LCH-ND) without other sites of active LCH.
Patients <21 years with other histiocytic disorders (Grp3)	Cobimetinib	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.
Patients ≥ 21 years with LCH/histiocytic disorders (Grp4)	Cobimetinib	Adults (≥21 years) with LCH or other histiocytic disorder with recurrent active lesions (may also have LCH-ND).

Primary Outcome Measures

Name	Time	Method
Overall Response Rates using modified RECiST criteria	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 Outcome Measures

Name	Time	Method
Progression Free Survival	12 months	Progression Free Survival defined as the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse.
Nature and Severity of Adverse Events	12 months	Assessment of the nature and severity of adverse events in patients treated with Cobimetinib for histiocytic disorders.

Trial Locations

Locations (11)

John Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Children's Medical Center- UTSW; 🇺🇸 Dallas, Texas, United States

Dana Farber Cancer Institute, Boston Children's; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Children's National Hospital; 🇺🇸 Washington, District of Columbia, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

NACHO Consortium; 🇺🇸 Memphis, Tennessee, United States

University of Wisconsin-American Family Children's Hospital; 🇺🇸 Madison, Wisconsin, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States