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Langerhan's Cell HistiocytosisPhase 2NACHO-COBINCT04079179

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

A Phase 2 study testing Cobimetinib in people with Langerhan's Cell Histiocytosis and Juvenile Xanthogranuloma, run by Carl Allen at 12 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Cobimetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
12 sitesUnited States
Study dates
19 Apr 2021to Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • As of 27Feb2026, due to suspension no longer being available, subject must be able to swallow tablets.
  • -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.
  • Performance Level:
  • -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.
  • Adequate Hematologic Function Defined as:
  • ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
  • Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
  • Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
  • Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
  • Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed).
  • Adequate Renal Function Defined as:
  • Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows:
  • Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/dL, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4;
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
  • Serum albumin ≥ 2 g/dL.
  • For patients with liver disease caused by histiocytic disorder:
  • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease.
  • Adequate Cardiac Function Defined as:
  • Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above
  • Pregnancy/Birth Control
  • Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
  • Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control.

Who cannot join

  • 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.
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  • Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
  • 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.
  • Exclusions for other illness
  • Other active malignancy or history of secondary malignancy.
  • Refractory nausea and vomiting, malabsorption, external biliary shunt
  • Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
  • Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
  • History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
  • History of pneumonitis.
  • Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
  • History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
  • Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
  • History of clinically significant cardiac dysfunction, including the following:
  • Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
  • Unstable arrhythmia
  • Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
  • Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
  • Myocardial infarction within 3 months prior to initiation of study treatment
  • Known chronic human immunodeficiency virus (HIV).
  • History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
  • Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
  • As of 27Feb2026, children less than 20 kg, due to discontinuation of suspension formulation.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Carl E Allen, MD, PhD contact

832-822-4242

ceallen@texaschildrens.org

Olive Eckstein, MD contact

832-822-4242

Eckstein@bcm.edu

12 sites in 1 country

United States12 sites, 11 recruiting

  • John Hopkins University School of Medicine

    Baltimore, Maryland, 21287

    Elias T Zambidis, MD PhD, (410) 614-0123, Ezambid1@jhmi.edu

    Recruiting

  • Dana Farber Cancer Institute, Boston Children's

    Boston, Massachusetts, 02215

    Barbara Degar, MD, 617-632-5186, barbara_degar@dfci.harvard.edu

    Sara Galinko, 617-632-6644, Sara_galinko@dfci.harvard.edu

    Recruiting

  • Children's Medical Center- UTSW

    Dallas, Texas, 75235

    Erin Butler, MD, 214-648-6332, erin.butler@utsouthwestern.edu

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Carl E. Allen, MD, PhD, 832-826-0860, ceallen@txch.org

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

    Kevin Bielamowicz, 501-364-1494, kjbielamowicz2@uams.edu

    Recruiting

  • University of Wisconsin-American Family Children's Hospital

    Madison, Wisconsin, 53792

    Terminated

  • NACHO Consortium

    Memphis, Tennessee, 38105

    Sara Clyburn, 901-595-6042, Sara.Clyburn@STJUDE.ORG

    Heidi Clough, 901-595-0362, Heidi.Clough@STJUDE.ORG

    Not yet recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Christopher Forlenza, 212-639-5226, forlenzc@mskcc.org

    Recruiting

  • Children's Hospital of Orange County

    Orange, California, 92868

    Lilbeth Torno, MD, 714-509-4348, LTORNO@choc.org

    Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Laura Retson, MD, (602) 933-0920, Lretson@phoenixchildrens.com

    Recruiting

  • UCSF Benioff Children's Hospital

    San Francisco, California, 94158

    Karina Wong, 415-298-9434, Karina.Wong@ucsf.edu

    Mahum Kudia, 415-290-1053, Mahum.Kudia@ucsf.edu

    Recruiting

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

    Birte Wistinghausen, MD, 2024762800, bwistingha@childrensnational.org

    Recruiting

Other trials in United States

About this study

Official title: 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.

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.

Read the 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.

Being tested
Cobimetinib
Keywords
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Medical subject headings
Histiocytosis, Langerhans-Cell, Xanthogranuloma, Juvenile, Erdheim-Chester Disease, Histiocytosis, Sinus, Histiocytic Sarcoma, Histiocytic Disorders, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobimetinibDrug

    Also called COTELLIC, RO5514041

    Cobimetinib will be administered at a maximal dose of 60 mg daily for patients <18 years old and a flat dose of 40 mg daily for patients ≥18 years for 21 days on, then 7 days off, in a 28-day treatment cycle for a total of 12 cycles (approximately 12 months).

Study groups in NCT04079179
Study groupRoleWhat they receive
Patients < 21 years with recurrent LCH (Grp1)ExperimentalChildren (≥ 6 months) and young adults (<21 years) with recurrent active LCH lesions (may also have LCH-ND).
Receives: Drug: Cobimetinib
Patients of any age with LCH-ND (Grp2)ExperimentalPatients of any age (≥ 6 months) with progressive LCH Neurodegenerative Disease (LCH-ND) without other sites of active LCH.
Receives: Drug: Cobimetinib
Patients <21 years with other histiocytic disorders (Grp3)ExperimentalNewly 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.
Receives: Drug: Cobimetinib
Patients ≥ 21 years with LCH/histiocytic disorders (Grp4)ExperimentalAdults (≥21 years) with LCH or other histiocytic disorder with recurrent active lesions (may also have LCH-ND).
Receives: Drug: Cobimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rates using modified RECiST criteria

    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.

    Measured: 12 months

Secondary outcomes (2)

  1. Progression Free Survival

    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.

    Measured: 12 months

  2. Nature and Severity of Adverse Events

    Assessment of the nature and severity of adverse events in patients treated with Cobimetinib for histiocytic disorders.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Sep 2019
  2. Study start19 Apr 2021
  3. Primary completionJan 2028 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Participants are assigned to one of 4 groups in parallel for the duration of the study.
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04079179
Sponsor's protocol ID
H-43475 NACHO COBI
Acronym
NACHO-COBI
Status last verified
Oct 2026
First submitted
10 Aug 2019
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cobimetinib in people with Langerhan's Cell Histiocytosis and Juvenile Xanthogranuloma, run by Carl Allen at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Carl E Allen, MD, PhD (832-822-4242, ceallen@texaschildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rates using modified RECiST criteria (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04079179.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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