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Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders | Clinical Trials | Clareo Health

RECRUITINGPHASE2

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

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.

NCT04079179•Carl Allen

View on ClinicalTrials.gov

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.

Eligibility

Age

All ages

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Age at study entry
•For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
•For Group 2: Participant may be at least 6 months of age at the time of enrollment
•For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
•For Group 4: Participant must be 21 years of age or older at the time of enrollment
•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 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.
+22 more criteria

Exclusion Criteria

•\- Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
•Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately. See below for specific consideration of prednisone and corticosteroids prior to enrollment.
•* Radiation therapy within the 14 days prior to enrollment.
•* Any prior treatment with Cobimetinib.
•* Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
•* Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or \< 5 half-lives, whichever is longer, prior to study enrollment.
•* For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
•* Corticosteroid therapy less than or equal to 0.5 mg/kg/day averaged during the 28 days prior to study enrollment is permissible. Patients receiving corticosteroids must be on a stable or decreasing dose for 14 days prior to enrollment and discontinue once study treatment has started.
•* Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
•* Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
+17 more criteria

Locations (12)

Phoenix Children's Hospital

Phoenix, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

John Hopkins University School of Medicine

Baltimore, Maryland, United States

Dana Farber Cancer Institute, Boston Children's

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

NACHO Consortium

Memphis, Tennessee, United States

Children's Medical Center- UTSW

Dallas, Texas, United States

Key Dates

Start Date

April 19, 2021

Primary Completion Date

December 1, 2025

Completion Date

December 1, 2029

Last Updated

September 18, 2025

Enrollment

ESTIMATED participants

Conditions

Langerhan's Cell HistiocytosisJuvenile XanthogranulomaErdheim-Chester DiseaseRosai Dorfman DiseaseNeuro-Degenerative DiseaseHistiocytic SarcomaHistiocytic Disorders, Malignant

Interventions

Cobimetinib

DRUG

Contacts

Carl E Allen, MD, PhD

CONTACT

832-822-4242 ceallen@texaschildrens.org

Olive Eckstein, MD

CONTACT

832-822-4242 Eckstein@bcm.edu

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 18, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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