Treatment Optimization for Children with De Novo and Relapsed Langerhans cell Histiocytosis (LCH) as Part of the International Collaborative Study LCH IV

• Applicant: Professor Dr. Thomas Lehrnbecher
• Subject Area: Pediatric and Adolescent Medicine ; Hematology, Oncology
• Term: from 2016 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280500934

Langerhans cell Histiocytosis (LCH) is a malignant disorder affecting 3-5/1 million children. Previous trials decreased mortality by intensifying induction chemotherapy, but up to 40% of patients with LCH still reactivate, and permanent sequelae occur in up to 50% of patients. The proposed phase III open-label multicenter randomized trial will evaluate strategies of maintenance therapy [prolongation (12 vs 24 months)±intensification with 6-mercaptopurine] in all patients with de novo LCH (Stratum I) and will evaluate a new compound (indomethacin) in patients with relapsed LCH (Stratum II) to decrease relapse rate and permanent morbidity. Primary endpoint is reactivation-free survival, secondary endpoints include toxicity and risk of permanent consequences. Although many patients suffer from significant morbidity, LCH is a rare disease. Germany alone does not have enough patients for a sufficiently powered study, which has therefore to be done in an international setting. A collaborative trial (LCH-IV) has already started in several countries, and the participation of Germany in the frame of the proposed study is necessary, as Germany is expected to enroll >20% of all patients. This trial may ultimately decrease the risk of relapse and permanent sequelae, thus improving quality of life and reducing socio-economic burden in patients with LCH.

• DFG Programme: Clinical Trials