Trial Aims to Expand Access to Targeted Therapy Drug for LCH

A team led by Ashish Kumar, MD, PhD, within Cincinnati Children’s Cancer and Blood Diseases Institute, anticipates that findings from a phase II prospective clinical trial will help make the case for wider accessibility and availability of a novel MEK inhibitor for Langerhans cell histiocytosis (LCH) and related histiocytic disorders.

Kumar and Allison Bartlett, MD, co-directors of Cincinnati Children’s Histiocytosis Center, are serving as the lead principal investigators of the trial, which is designed to study the efficacy of mirdametinib for LCH and related disorders—including juvenile xanthogranuloma (JXG), Rosai-Dorfman disease (RDD) and Erdheim-Chester disease (ECD).

Researchers believe inhibitors such as mirdametinib are at least as effective as, and likely more effective than, chemotherapy, which is the standard of care. They note that early data also show the inhibitor causes fewer side effects in patients.

Currently, Cincinnati Children’s is the only hospital in the nation offering this treatment, and the only site where patients can enroll in the clinical trial.

Understanding the Limits of Chemotherapy in Histiocytic Disorders

LCH is a rare blood disorder that’s more common in children than adults. It affects about one of every 200,000 children. Most often, LCH is diagnosed between the ages of 1 and 3.

In some cases, LCH can affect organs such as the liver, spleen and bone marrow, as well as the central nervous system. In these patients—called risk-organ-positive (RO+) LCH patients—the risk of serious illness and death is high. However, in many patients, especially those with RO+ LCH, the disease doesn’t respond to chemotherapy. Of the patients who do respond, many suffer disease progression after initial therapy response or recurrence after therapy completion.

“In LCH and related disorders, the efficacy of chemotherapy is, at best, 50%,” Kumar says. “That means at least half, and sometimes even more than half, of patients will suffer a recurrence of the disease. And the recurrence can have potential lifelong, permanent consequences, such as liver failure, pituitary dysfunction and brain damage.” 

For these reasons, Kumar and fellow researchers began searching for alternatives to chemotherapy several years ago.

“Thanks to the research done in the biology of these diseases, we knew that there were alternative targeted therapies available, which we have been using off-label ad hoc for the last few years,” he says, noting the use of other MEK inhibitors for LCH, such as dabrafenib and trametinib.

The initial responses in patients who were given inhibitors (dabrafenib or trametinib) after their disease had progressed or recurred after chemotherapy were “so dramatic and so great,” it prompted Kumar and his team to use the inhibitors more frequently.

“I started asking why we were making children, or even adults for that matter, fail chemotherapy before offering them this novel therapy that seems to be at least as good as chemotherapy if not better and easier to handle,” he says. “But most important for me was the ability to keep the disease under control.”

Designing a Trial With Patients and Families in Mind

The trial began enrolling patients in February 2024. As of today, eight patients are enrolled. Recruitment is ongoing. The trial is open to both adult and pediatric patients, aged 2 and above, from anywhere in the country, with any histiocytic disorder—whether it’s newly diagnosed or recurrent. 

Right now, children under the age of 2 are not eligible for the trial, but Kumar and Bartlett hope they’ll soon have enough data on the therapy’s safety to treat younger children. 

Although the trial is currently only available at Cincinnati Children’s, the study is designed to reduce the cost and travel burden on patients and families.  

“We intentionally designed the trial so families have to make, at most, seven trips to Cincinnati Children’s over a two-year period,” Kumar says, “and we are actively seeking funding from grants to offset the costs of travel for families. We’re trying to make it as easy on them as possible.” 

The research team is also collaborating with patients’ physicians at the local level, so most evaluations can be performed close to a family’s home.

Learn more about the trial or contact Ashish.Kumar@cchmc.org for more information. 

(Published March 2026)

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