Langerhans cell histiocytosis
Conditions
Interventions
Children and adolescents with LCH need to be treated. Treatment is based on the
different strata as named in the background and in the protocol. The protocol
is the internationally accepted guidelin
Sponsors
Stichting Kinderoncologie Nederland
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: * Definitive diagnosis of Langerhans cell histiocytosis * Age less 18 years at time of definitive diagnosis * Met inclusion criteria for the respective stratum * Signed written informed consent
Exclusion criteria
Exclusion criteria: Exclusion criteria are stratum specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints are different for the different strata, therefore listed per stratum here. Stratum I & II: Reactivation- free survival Stratum III: The response will be evaluated at 4-5 weeks from the initiation of the second cycle (about 9-10 weeks from start of Stratum III). Stratum IV: To determine the overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT) Stratum V: To study the course of ND-CNS-LCH (both radiological and clinical neurodegeneration) * To study the impact of 2-CdA on the response of isolated tumorous CNS lesions. Stratum VI: Reactivation-free survival Stratum VII: Cumulative incidence of specific permanent consequences (PC) e.g. diabetes insipidus (DI), growth hormone deficiency (GHD), neuropsychological impairment | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints are different for the different strata, therefore listed per stratum here. Stratum I: * Overall survival * Incidence of permanent consequences * Toxicity of treatment * The proportion of patients alive and free of disease without permanent consequences * Cumulative incidence of reactivations in risk organs Stratum II: To determine the response rate to the combination of prednisone, vincristine and cytarabine * The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, anterior pituitary dysfunction, radiological or clinical neurodegeneration) * To describe treatment-related toxicities * To compare reactivation rates after continuation treatment with Indomethacin vs. 6-MP/MTX. Stratum III: Time to complete disease resolution (Non-Active Disease) - The type of subsequent intensive and/or maintenance therapy utilized - The early and late mortality - The early and late toxicity Stratum IV: To determine d+100 transplant related mortality, * To determine the incidence of hematopoietic recovery, and donor chimerism at d+100 and 1 year post RIC-HSCT * To determine the incidence of grades II-IV and III-IV acute GVHD, * To determine the incidence of chronic GVHD Stratum V: To assess whether systemic therapy can be beneficial for patients with clinically manifest ND-CNS-LCH * To assess the role of 2-CdA in preventing ND-CNS-LCH in patients with isolated tumorous CNS-LCH * To study the efficacy of intravenous immunoglobulin and intravenous cytarabine in the treatment of ND-CNS-LCH (by both radiological and clinical assessment) * To assess markers of neurodegeneration and LCH activity in the spinal fluid of patients who have diabetes insipidus as well as patients with radiologic and/or clinical signs of CNS-LCH Stratum VI: Need for systemic therapy later during disease course * Spectrum and cumulative incidence of permanent consequences Stratum VII: Identify possible risk facto | — |
Countries
Netherlands
Outcome results
None listed