Treatment of Langerhans Cell Histiocytosis in Children

Summary description of the study

Due to the complexity of the manifestations and consequences of Langerhans Cell Histiocytosis (LCH), the aim of the LCH-IV study is to tailor treatment to the characteristics at diagnosis (whether the disease affects risk organs or not, one or multiple organs) and to the patients' response to treatment. The following 7 patient classes are distinguished. -Class I: Primary therapy for LCH patients when multiple organs are affected (Group 1) and when bones show multiple lesions or the central nervous system shows "risky" lesions (Group 2) -Class II: Secondary therapy when no risk organs are affected and when patients do not respond to primary therapy or when a relapse occurs after primary therapy. -Class III: Salvage therapy when risk organs are affected and show dysfunction and patients do not respond to primary therapy -Class IV: Stem cell transplantation when risk organs show dysfunction and patients do not respond to primary therapy -Class V: Monitoring and treatment of isolated tumors and neurodegenerative LCHs that affect the central nervous system -Class VI: Natural history and management of "other" LCH patients, in whom one organ is affected and who do not need systemic therapy at the time of diagnosis. -Class VII: Long-term follow-up for all patients, regardless of the form of therapy used. After complete resolution of the disease and completion of therapy, patients are examined for possible relapses of the disease and long-term consequences.

(BASEC)

Intervention under investigation

-Class I Group 1

Patients receive an initial treatment with the medications Vinblastine and Prednisone for the first 6 weeks.

If the response is good but not total, or if the disease remains stable, patients receive a second initial treatment.

(Patients whose disease has not improved after 6 or 12 weeks of initial treatment move to another patient class.)

Afterward, patients receive maintenance treatment for 1 or 2 years with the medications Vinblastine, Prednisone with or without 6-Mercaptopurine. (The 4 treatment options are assigned randomly = randomized.)

-Class I Group 2

Patients receive an initial treatment with the medications Vinblastine and Prednisone for the first 6 weeks.

If the response is good but not total, or if the disease remains stable, patients receive a second initial treatment. (Patients whose disease has worsened after the initial treatment move to another patient class.)

Afterward, patients receive maintenance treatment for 6 or 12 months with the medications Vinblastine and Prednisone. (These 2 options are assigned randomly = randomized.)

-Class II

Patients receive an initial treatment with the medications Prednisone, Cytarabine, and Vincristine for the first 24 weeks.

If the response is good but not total, or if the disease remains stable, patients receive a second initial treatment.

(Patients whose disease has worsened after the initial treatment move to another patient class.)

Afterward, patients receive maintenance treatment for 18 months with the medications Indomethacin or 6-Mercaptopurine plus Methotrexate. (The 2 treatment options are assigned randomly = randomized.)

-Class III

Patients receive two courses of treatment with the medications Cladribine and Cytarabine during the first 8 weeks.

If the response is total, patients receive part 2 and then part 3 of the maintenance treatment.

Part 2: Patients receive the medications Vinblastine, Prednisone, 6-Mercaptopurine, and Methotrexate for 6 months.

Part 3: Patients receive the medications 6-Mercaptopurine and Methotrexate for 12 months.

If the response is good but not total, patients start the maintenance treatment with part 1.

Part 1: Patients receive the medication Cladribine for 6 weeks.

Afterward, these patients receive parts 2 and 3 of the maintenance treatment.

If the degree of the disease remains unchanged, up to 4 cycles of the medications Cladribine and Cytarabine may be administered.

If the disease worsens, an allogeneic stem cell transplantation (Class IV) is recommended.

-Class IV

This involves an allogeneic stem cell transplantation. However, a series of preliminary examinations (e.g., bone marrow puncture, computed tomography, lung, heart, and kidney function tests, etc.) must be performed beforehand.

Patients are admitted to the transplant unit two weeks before the transplantation and are decontaminated. They receive a central venous access for the medications.

The patients' immune system is suppressed with the medications (Alemtuzumab, Fludarabine, Melphalan, Cyclosporine A, and Mycophenolate Mofetil). On the day of transplantation, the donor's stem cells are administered like a blood transfusion through the central venous catheter. Ten to twenty days after the stem cell transplantation, the transplanted stem cells grow in the bone marrow and begin to form new blood cells.

-Class V

For patients with isolated tumors, the medication Cladribine is used. The medication is administered every four weeks, depending on the response, two to six times.

For patients without tumors but with clinical signs of a disease in the central nervous system,

(BASEC)

Disease under investigation

Langerhans Cell Histiocytosis (LCH), tumor-like lesions with proliferation of certain immune cells in connective tissue

(BASEC)

Sponsor

not available

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

not available

Date of authorisation

18.05.2026

(BASEC)

Results of the trial