Dabrafenib or Trametinib plus Clofarabine for high-risk or relapsed pediatric Langerhans cell histiocytosis

A Real-world Investigation of the Combination of Darafenib or Trametinib and Clofarabine in the Treatment of High-risk, Recurrent, or Refractory Pediatric Patients With Langerhans Cell Histiocytosis.

This treatment will test whether adding a MAPK inhibitor (dabrafenib or trametinib) to the chemotherapy drug clofarabine helps children and teens (0–18) with high-risk, recurrent, or refractory Langerhans cell histiocytosis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 0 Years to 18 Years
• Sex: All
• Sponsor: West China Second University Hospital (Academic / other)
• Drugs / interventions: trametinib, chemotherapy, prednisone, fludarabine
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07022834 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional program using either dabrafenib or trametinib (MAPK pathway inhibitors) combined with clofarabine (a nucleoside analogue) to treat children with high‑risk or relapsed LCH, especially those with liver, spleen, or hematopoietic involvement. Eligible patients are 0–18 years old with CD1a+/CD207+ LCH who have had disease progression or reactivation after prior chemotherapy or targeted therapy and meet organ‑function and performance criteria. Patients will receive the combination therapy with regular monitoring for response, toxicity, and predefined exit criteria such as progression at three months or severe clofarabine toxicity. The work is conducted in a real‑world clinical setting at West China Second University Hospital with consented follow‑up and safety oversight.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents (0–18) with CD1a+/CD207+ LCH involving liver, spleen, or hematopoietic sites, who have progressed or relapsed after prior chemotherapy or targeted therapy and have adequate organ function and performance status.

Not a fit: Patients with severe comorbidities (eg, uncontrolled heart or kidney failure, active hepatitis or HIV, recent transplant), secondary tumors, ongoing nephrotoxic drug use, unresolved severe toxicity from recent therapies, or known allergy to the study drugs are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, the combination could increase remission rates and reduce relapses and mortality in children with high‑risk or treatment‑resistant LCH.

How similar studies have performed: MAPK inhibitors and nucleoside analogs have shown benefit in refractory LCH and lowered mortality in prior work, but combining a MAPK inhibitor specifically with clofarabine is a newer approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Children aged 0-18 with LCH (CD1a+/CD207+);
2. Initial LCH diagnosis with hematopoietic, liver, or spleen involvement;
3. LCH patients with disease progression or reactivation after chemotherapy (e.g., prednisone, vincristine, cytarabine, clarithromycin) or targeted therapy;
4. Consent to treatment and follow-up;
5. ECOG score ≥ 2, Lansky score ≥ 50, organ function suitable for chemotherapy.

Exclusion Criteria:

1. Other underlying diseases (e.g., primary immunodeficiency, heart/kidney failure, hepatitis, HIV, organ transplant);
2. Secondary tumor;
3. Recent chemotherapy, radiotherapy, or MAPK inhibitor use with lingering adverse effects;
4. Ongoing nephrotoxic drug use;
5. Refusal to consent.

Exit Criteria:

1. Allergies to dabrafenib or trametinib and clofarabine；
2. Disease progression after 3 months on dabrafenib or trametinib；
3. Severe toxic side effects from clofarabine (grade 4 non-infectious non-hematological toxicity, SIRS, capillary leak syndrome)； 4）The doctor recommends halting the current treatment plan for the patient's benefit.

Where this trial is running

Chengdu, Sichuan

• Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, Chengdu, China — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Xue Tang, MD

Conditions Langerhans Cell Histiocytosis