CH-IV Treatment Protocol for Children and Adolescents with LANGERHANS CELL HISTIOCYTOSIS

Phase 1

• Conditions: angerhans cell histiocytosis; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-001699-20-NL
• Lead Sponsor: St. Anna Kinderkrebsforschung

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-12-23
• Last Update Posted: 14 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1400

Inclusion Criteria

•Stratum I:
Patients must be less than 18 years of age at the time of diagnosis;
Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis;
No prior systemic therapy for LCH, except systemic steroids given up to one week;
Signed informed consent;
•Stratum II:
Patients of Stratum I who have proressive disease (AD worse) in nonrisk organs after Initial Course 1,
AD intermediate or worse in non-risk organs or AD better in risk organs after Initial Course 2,
AD intermediate or worse, who do not meet organ dysfunction eligibility criteria (acc. table XI) at any time of Stratum I Treatment,
Disease progression (AD worse) in non-risk organs at any time during
continuation treatment,
Active disease at the end of Stratum I treatment,
Disease reactivation in non-risk organs at any time after completion of Stratum I treatment,
Disease reactivation in risk-organs, who do not meet organ dysfunction criteria (acc. table XI) at any time or after completion of Stratum I Treatment,
Signed informed consent,
•Stratum III
Patients from Stratum I who fulfill the following criteria:
AD intermediate or worse in risk organs after after Initial Course 1, or
AD worse or AD intermediate in risk organs after Initial Course 2,
Presence of unequivocally severe organ dysfunction (hematological
dysfunction, liver dysfunction, or both of them),
Signed informed consent;
•Stratium IV:
Patients from Stratum I or Stratum III who fulfill the following criteria:
AD worse in risk organs after week 6 (after Initial Course 1), or AD
worse or AD intermediate in risk organs after after Initial Course 2 of
Stratum I, or
AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD
worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum
III, and
Presence of unequivocally severe organ dysfunction,
Informed consent available,
Adequate organ function
•Stratum V:
All patients with verified diagnosis of LCH and MRI findings consistent with neurodegenerative (ND) CNS-LCH irrespective of previous treatments,
Patients with isolated tumorous CNS-LCH (including isolated DI with
mass lesion in the hypothalamus-pituitary axis),
Signed informed consent
•Stratum VI
Patients with newly diagnosed single-system LCH (other than mfb,
isolated tumorous CNS-LCH, or isolated CNS-risk lesion,
Signed informed consent;
•Stratum VII:
All patients registered in LCH IV as long as consent for long-term follow-up has not been witheld
Are the trial subjects under 18? yes
Number of subjects for this age range: 1400
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Stratum I:
Pregancy (patients of child-bearing age must be appropriately tested before chemotherapy);
LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease;
Prior systemic therapy, except systemic steroids given up to one week;
•Stratum II
Patients with progressive disease in risk organs,
Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations,
No written consent of the patient or his/her parents or legal guardian
•Stratum III:
Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement;
Inadequate renal function as defined by serum creatinine > 3x normal for age;
•Stratum IV:
Pulmonary failure (requiring mechanical ventilation) not due to active LCH;
Isolated liver sclerosis or pulmonary fibrosis, without active LCH;
Uncontrolled active life-threatening infection;
Decreased renal function with a GFR of less than 50ml/1.73m2/min;
Pregnancy or active breast feeding;
Failure to provide signed informed consent;
•Stratum V:
Patients without any evidence of isolated tumorous CNS-LCH lesions or ND-CNS lesions
•Stratum VI:
Patients with single-system LCH who have an isolated tumorous CNS lesion (eligible for Stratum V);
Patients with isolated CNS-risk or mfb lesion (eligible for Stratum I, Group 2);
•Stratum VII:
no consent for long-term follow up available

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified