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

Phase 3

Recruiting

Conditions: C96.0
C96.5
C96.6
Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis [Letterer-Siwe disease]
Multifocal and unisystemic Langerhans-cell histiocytosis
Unifocal Langerhans-cell histiocytosis

Registration Number: DRKS00012701

Lead Sponsor: Johann Wolfgang Goethe-Universität Frankfurt am Main

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

Stratum I:
•Age: Patients must be less than 18 years of age at the time of enrollment.
•No systemic therapy for LCH prior to the standardized induction therapy, e.g., prior to Initial Course 1 (IC-1) and, eventually, Initial Course 2 (IC-2) (pre-study)
•Evaluation demonstrates non-active disease after IC-1 (independent of involvement of risk organs) or non-active disease or active disease better (only for patients without involvement of risk organs) after IC-2 [imaging studies need to be referenced regarding treatment response to initial course(s) (pre-study)]

Stratum II:
•Age: Patients must be older than 2 years and less than 18 years of age at the time of enrollment
•No systemic therapy for progression/relapse of LCH prior to the standardized second line therapy, e.g., standardized 24-week second-line initial course (SL-IT), which is NOT part of the study
•Evaluation demonstrates non-active disease or active disease better after SL-IT [imaging studies need to be referenced regarding treatment response to second-line initial course (pre-study)].

Both Strata:
•Patients must have a referenced histological verification of the diagnosis of LCH (pre-study)
•Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception (e.g., barrier contraception for males, contraceptive pill (Pill”) for female) throughout the study and for at least 90 days (male subjects) and 30 days (female subjects) after the last dose of assigned study treatment.
•Signed informed consent of parent(s)/legal guardian(s) and/or patient (when applicable depending on age and patient’s compliance) prior to any protocol procedure

Exclusion Criteria

Stratum I:
•Patients with any active disease after IC-1 or patients with active disease intermediate/worse (for patients without involvement of risk organs) or any active disease (for patients with involvement of risk organs) after IC-2
•Hypersensitivity for one of the trial drugs or any of its excipients or hypersensitivity to any other vinca-alkaloid or any of its excipients
•Leukopenia, which is not caused by LCH
•Severe uncontrolled infection
•Stomatitis or ulcera of the gastrointestinal tract
•Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
•Breastfeeding
•Participation in other clinical trials according to German drug law (§§40ff AMG)

Stratum II:
•Patients with progressive disease in risk organs
•Patients with active disease intermediate/worse after second-line intensive course
•Hypersensitivity for one of the trial drugs or any of its excipients
•Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy
•Breastfeeding
•History of severe bleeding, ulcera of the gastrointestinal tract, history of CNS bleeding or other bleeding disorders unrelated to LCH
•Patient suffering from Crohn´s disease or Colitis ulcerosa
•History of asthma, urticaria, or other allergic-type reactions after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
•Known severe immunodeficiency, untreated blood disorders not caused by LCH or untreated functional disorders of the hematopoietic system*
•Severe impairment of liver, chronic liver disease, increased alcohol consumption
•Renal impairment (creatinine-clearance < 60 ml/min)
•Heart insufficiency
•Severe uncontrolled infection
•Participation in other clinical trials according to German drug law (§§40ff AMG)
*Note: Both LCH and preceding chemotherapy for LCH, which is mandatory for the cure of the patient, may cause blood disorders/functional disorders of the hematopoietic system as well as clotting disorders. This is similar to other hematological diseases such as acute lymphoblastic leukemia, in which standard treatment consists of cytotoxic agents such methotrexate. Therefore, the inclusion of patients with blood disorders unrelated to LCH depends on the careful evaluation of the treating investigator, if the patient is in stable condition and the disorder is sufficiently treated.

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
•Reactivation-free survival

Secondary Outcome Measures

Name	Time	Method
Stratum I, Group 1 and 2<br>•Overall survival<br>•Incidence of permanent consequences (Diabetes insipidus, neurodegeneration)<br>•The proportion of patients alive and free of disease without permanent consequences<br>•Cumulative incidence of reactivations in risk organs <br>•Treatment-related toxicity<br>Stratum II:<br>•Overall survival<br>•The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, radiological or clinical neurodegeneration)<br>•Incidence of reactivation of the disease in the experimental arm<br>•Treatment-related toxicity<br>