Mirdametinib in Histiocytic Disorders

NCT06153173 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2021-0206
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Langerhans Cell Histiocytosis (LCH); Juvenile Xanthogranuloma (JXG); Rosai-Dorfman Disease (RDD); Histiocytic Disorders

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year (completion of 13 four week cycles)

Secondary Outcomes (4)

• Duration of response to mirdametinib

  2 years (completion of 26 four week cycles)

• Maximum Plasma Concentration (Cmax)

  Day 1 of the first 5 four week cycles)

• Time to peak drug concentration (Tmax)

  Day 1 of the first 5 four week cycles)

• Area under the plasma concentration time curve (AUC)

  Day 1 of the first 5 four week cycles)

Study Arms (1)

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).

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

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.

Mirdametinib

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell; Xanthogranuloma, Juvenile; Histiocytosis, Sinus

Interventions

mirdametinib

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Ashish Kumar, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Allison Bartlett, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Trapp

CONTACT

(513) 803-8574; monica.trapp@cchmc.org

Caitlin Cottrell

CONTACT

(513) 803-7039; Caitlin.Cottrell@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2023
• First Posted: December 1, 2023
• Study Start: February 5, 2024
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (1)