Langerhans Cell Histiocytosis (LCH)Phase 2NCT06153173
Mirdametinib in Histiocytic Disorders
A Phase 2 study testing Mirdametinib in people with Langerhans Cell Histiocytosis (LCH) and Juvenile Xanthogranuloma (JXG), run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The purpose of this study is to see if treatment with mirdametinib in patients with Langerhans cell histiocytosis (LCH) or other histiocytic disorders will be better than current treatments and with fewer side effects. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Langerhans Cell Histiocytosis (LCH), Juvenile Xanthogranuloma (JXG), Rosai-Dorfman Disease (RDD)
- What is being tested?
- Mirdametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2024to Mar 2031
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects must be ≥ 2 years of age AND have a diagnosis of a histiocytic disorder that requires systemic therapy
- If patient has had a diagnostic biopsy, biopsy must be reviewed and confirmed by CCHMC pathologist as feasible
- If patient has had a biopsy but has not had molecular testing done, must have tissue available for mutational analysis
- If patient has isolated pituitary/CNS disease or situations where biopsy is not feasible, positive ddPCR blood test for mutation associated with histiocytic neoplasm with clinical features of histiocytosis is sufficient
- Must have measurable disease on PET scan or brain MRI
- Subjects must demonstrate adequate organ function as defined:
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- Renal: maximum serum creatinine 2x the upper limit of normal (ULN) OR a creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2
- Liver: ALT ≤ 3x ULN AND normal INR (≤ 1.5)
- Hematologic: Hematology: Albumin ≥ 2.8 g/dL; Absolute neutrophil count ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L; Hemoglobin ≥ 9.0 g/dL
- Patients with organ function abnormalities outside of these thresholds deemed to be the result of histiocytic disease will be considered eligible
Who cannot join
- Prior therapy with stipulations as described:
- Myelosuppressive Chemotherapy: Must not have received any cytotoxic chemotherapy which impacts the growth and development of cells in the bone marrow within 14 days of enrollment onto this study (i.e. cytarabine, cladribine, clofarabine, mercaptopurine, methotrexate, vinblastine)
- MEK Inhibitors: Must not have received a MEK inhibitor within 30 days (or 5 half-lives, whichever is longer) of enrollment, NOR have had disease progression on MEK inhibitor
- Steroids: Due to the increased risk of an ocular event, the use of systemic oral, inhaled, or ocular glucocorticoid therapy is prohibited within 14 days prior to first dose of mirdametinib. Throughout the treatment period, short term glucocorticoid treatment (30 days or less) is permitted. Any patients requiring long-term steroid use (more than 30 consecutive days) are not eligible. The exception to this rule is subjects with endocrine deficiencies who require physiologic steroids
- Radiation: Must not have received radiation within 14 days of study enrollment or have received radiation to the orbit at any time
- Risk factors for retinal vein occlusion (RVO) are listed. Exclusion should be considered by clinical discretion if they have any of the following risk factors for RVO at screening:
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- Intraocular pressure (IOP) > 21 mmHg; if IOP is unable to be obtained (eg age, cooperation, tolerability), ophthalmologist's exam findings and overall assessment will be utilized. If in the ophthalmologist's assessment there are no signs of raised IOP, the subject will be considered eligible for this parameter
- Glaucoma or any significant abnormality (≥ grade 2) on ophthalmologic exam that is uncontrolled with intervention
- Serum cholesterol > 300 mg/dL
- Serum triglycerides > 300 mg/dL
- Hyperglycemia (either fasting blood glucose > 125 mg/dL OR random blood glucose > 200 mg/dL)
- Uncontrolled hypertension (participants ≤ 12 years of age with a blood pressure ≥ 95th percentile for age + 12 mmHg; participants ≥ 13 years of age with a blood pressure ≥ 140/90 mm Hg) unresolved on repeat measurement
- LVEF < 55% at screening OR history of clinically significant cardiac disease, unless deemed to be the direct result of disease
- Subjects who are pregnant or breastfeeding, or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Monica Trapp, Monica.Trapp@cchmc.org
Caitlin Cottrell, caitlin.cottrell@cchmc.org
About this study
Official title: A Phase II Trial of the MEK Inhibitor Mirdametinib in Histiocytic Disorders
The purpose of this study is to see if treatment with mirdametinib in patients with Langerhans cell histiocytosis (LCH) or other histiocytic disorders will be better than current treatments and with fewer side effects.
Read the detailed description
Langerhans cell histiocytosis (LCH) is a rare blood disorder. Though affecting all ages, LCH occurs more often in children, with an increased incidence in children less than 1 year of age. The disease presents in various ways, with most children suffering bony lesions, and skin rashes. In some patients, LCH affects vital organs such as liver, spleen, bone marrow, and the central nervous system. This group of patients are at significant risk of serious illness and death and are thus said to have risk-organ-positive (RO+) LCH. Current treatments for LCH consist of chemotherapy combined with other medications. However, many patients, especially those with RO+ disease, do not respond to therapy. Of the patients that do respond, many suffer progression of disease after an initial response to therapy, or recurrence of disease after completion of therapy.
The purpose of this study is to see if treatment with mirdametinib in patients with LCH or other histiocytic disorders will be better than current treatments and with fewer side effects.
- Conditions
- Langerhans Cell Histiocytosis (LCH), Juvenile Xanthogranuloma (JXG), Rosai-Dorfman Disease (RDD), Histiocytic Disorders
- Being tested
- Mirdametinib
- Medical subject headings
- Histiocytosis, Langerhans-Cell, Xanthogranuloma, Juvenile, Histiocytosis, Sinus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirdametinibDrug
Mirdametinib is administered by mouth twice daily on a continuous schedule, with each cycle being 4 weeks. Patients are instructed to take consecutive doses separated by a minimum of 6 hours and a maximum of 14 hours.
| Study group | Role | What they receive |
|---|---|---|
| Mirdametinib | Experimental | Mirdametinib will be dosed by mouth twice a day at a dose of 2 mg/m2 BID with a max of 4 mg BID (8 mg per day max). Receives: Drug: Mirdametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate to mirdametinib
Best overall response rate to mirdametinib after 13 four-week cycles as defined by positron emission tomography (PET) or magnetic resonance imaging (MRI) (for isolated pituitary/central nervous system (CNS) disease) response criteria.
Measured: 1 year (completion of 13 four week cycles)
Secondary outcomes (4)
Duration of response to mirdametinib
Duration of response to mirdametinib on study as defined by PET or MRI (for isolated pituitary/CNS disease) response criteria.
Measured: 2 years (completion of 26 four week cycles)
Maximum Plasma Concentration (Cmax)
Blood samples will be drawn for the pharmacokinetic profile before, and during mirdametinib therapy. Maximum plasma concentration will be calculated as data allow.
Measured: Day 1 of the first 5 four week cycles)
Time to peak drug concentration (Tmax)
Blood samples will be drawn for the pharmacokinetic profile before, and during mirdametinib therapy. Time to peak drug concentration (Tmax) will be calculated as data allow.
Measured: Day 1 of the first 5 four week cycles)
Area under the plasma concentration time curve (AUC)
Blood samples will be drawn for the pharmacokinetic profile before, and during mirdametinib therapy. Area under the plasma concentration time curve (AUC) will be calculated as data allow.
Measured: Day 1 of the first 5 four week cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2023
- Study start5 Feb 2024
- Primary completionMar 2030 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Langerhans Cell Histiocytosis (LCH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ashish Kumar, MD, PhD, Principal investigator, Children's Hospital Medical Center, CincinnatiAllison Bartlett, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06153173
- Sponsor's protocol ID
- 2021-0206
- Status last verified
- Sep 2026
- First submitted
- 11 Oct 2023
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of the MEK Inhibitor Mirdametinib in Histiocytic Disorders
- ClinicalTrials.gov ID
- NCT06153173
- Acronym / sponsor ID
- 2021-0206
- Conditions
- Langerhans Cell Histiocytosis (LCH), Juvenile Xanthogranuloma (JXG), Rosai-Dorfman Disease (RDD), Histiocytic Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 5 Feb 2024 (actual)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 1 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if treatment with mirdametinib in patients with Langerhans cell histiocytosis (LCH) or other histiocytic disorders will be better than current treatments and with fewer side effects.
Detailed description
Langerhans cell histiocytosis (LCH) is a rare blood disorder. Though affecting all ages, LCH occurs more often in children, with an increased incidence in children less than 1 year of age. The disease presents in various ways, with most children suffering bony lesions, and skin rashes. In some patients, LCH affects vital organs such as liver, spleen, bone marrow, and the central nervous system. This group of patients are at significant risk of serious illness and death and are thus said to have risk-organ-positive (RO+) LCH. Current treatments for LCH consist of chemotherapy combined with other medications. However, many patients, especially those with RO+ disease, do not respond to therapy. Of the patients that do respond, many suffer progression of disease after an initial response to therapy, or recurrence of disease after completion of therapy.
The purpose of this study is to see if treatment with mirdametinib in patients with LCH or other histiocytic disorders will be better than current treatments and with fewer side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mirdametinib | Experimental | Drug: MirdametinibMirdametinib will be dosed by mouth twice a day at a dose of 2 mg/m2 BID with a max of 4 mg BID (8 mg per day max). |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must be ≥ 2 years of age AND have a diagnosis of a histiocytic disorder that requires systemic therapy
- Must have measurable disease on PET scan or brain MRI
- Subjects must demonstrate adequate organ function as defined:
Key exclusion criteria (14 listed)
- Prior therapy with stipulations as described:
- Risk factors for retinal vein occlusion (RVO) are listed. Exclusion should be considered by clinical discretion if they have any of the following risk factors for RVO at screening:
- LVEF < 55% at screening OR history of clinically significant cardiac disease, unless deemed to be the direct result of disease
- Subjects who are pregnant or breastfeeding, or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirdametinibMirdametinib is administered by mouth twice daily on a continuous schedule, with each cycle being 4 weeks. Patients are instructed to take consecutive doses separated by a minimum of 6 hours and a maximum of 14 hours. | Drug | Mirdametinib |
Primary outcome
Response rate to mirdametinib
Time frame: 1 year (completion of 13 four week cycles)
Best overall response rate to mirdametinib after 13 four-week cycles as defined by positron emission tomography (PET) or magnetic resonance imaging (MRI) (for isolated pituitary/central nervous system (CNS) disease) response criteria.
4 secondary outcomes
Duration of response to mirdametinib
Time frame: 2 years (completion of 26 four week cycles)
Maximum Plasma Concentration (Cmax)
Time frame: Day 1 of the first 5 four week cycles)
Time to peak drug concentration (Tmax)
Time frame: Day 1 of the first 5 four week cycles)
Area under the plasma concentration time curve (AUC)
Time frame: Day 1 of the first 5 four week cycles)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
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Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
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Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders
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A Single-Arm,Multicenter Phase, Phase II Clinical Trial of Adebrelimab Combined With Trametinib in the Treatment of Refractory Recurrent Langerhans Cell Histiocytosis in Children and Adolescents
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ashish Kumar, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
Allison Bartlett, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mirdametinib in people with Langerhans Cell Histiocytosis (LCH) and Juvenile Xanthogranuloma (JXG), run by Children's Hospital Medical Center, Cincinnati at 1 site 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 10 inclusion and 14 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 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Monica Trapp ((513) 803-8574, monica.trapp@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate to mirdametinib (time frame: 1 year (completion of 13 four week cycles)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Sep 2026.