Evaluation of Efficacy and Tolerance of Cladribine in Symptomatic Pulmonary Langerhans Cell Histiocytosis

Study Overview
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Brief Summary
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ECLA is a phase II, multicenter study testing sub cutaneous cladribine 0.1mg/kg/j during 5 days, administrated every month for 4 courses, in symptomatic adult patients with pulmonary Langerhans cell histiocytosis and impairment of lung function patients.

Detailed Description
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ECLA is a phase II, multicenter study testing sub cutaneous cladribine 0.1mg/kg/j during 5 days, administrated every month for 4 courses, in symptomatic adult patients with pulmonary Langerhans cell histiocytosis and impairment of lung function patients.

Official Title
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Evaluation of Efficacy and Tolerance of Cladribine in Symptomatic Patients With Pulmonary Langerhans Cell Histiocytosis and Impairment of Lung Function

Conditions
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Langerhans Cell Histiocytosis of Lung

Intervention / Treatment
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* Drug: Cladribine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 to 55 yr Histologically proven pulmonary Langerhans cell histiocytosis ( patients with presumptive diagnosis whose lung function precludes lung biopsy may be included after revision of their medical record at the national reference center for Langerhans cell histiocytosis) Symptomatic pulmonary Langerhans cell histiocytosis (NYHA dyspnea class ≥2) with: irreversible airflow obstruction (FEV1/FVC<70%) with postbronchodilator FEV1 comprised between 30 and 70% of predicted and/or decrease ≥15% in FEV1, FVC or DLCO as compared to baselines values in the year preceding the inclusion Signed written informed consent Exclusion Criteria: Women at childbearing age without adequate contraception or wishing breastfeeding Male without adequate contraception during the study Dyspnea due to severe pulmonary arterial hypertension (PAP≥35mmHg) confirmed by cardiac right catheterism Previous malignancy Current infectious disease Renal failure Liver failure Severe alteration of lung Hematologic disease unrelated to Langerhans cell histiocytosis Epilepsy Hepatic, spleen or hematology involvement by Langerhans cell histiocytosis Pneumothorax within a month previously to inclusion Previous treatment with cladribine Contra indication to the use of cladribine Previous myelosuppressive treatment Simultaneous participation to another interventional clinical trial

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cladribine<br> | Drug: Cladribine<br>* Subcutaneous injections, 0,1 mg/kg/day for 5 days, one course per month for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated incidence of response to treatment | response to treatment after 6 months is defined as ≥10% improvement of forced vital capacity (FVC) and/or ≥10% improvement of postbronchodilator forced expiratory volume (FEV1) and ≥200ml | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responses to treatment |  | 3 months | 
| Absolute variations of FEV1, FVC, residual volume (RV), and Diffusing capacity of the lung for carbon monoxide (DLCO), (expressed in mL) |  | 6 months | 
| Grade 3 or 4 neutropenia or thrombopenia |  | 6 months | 
| Incidence of infection |  | 6 months | 
| Incidence of grade 3 or 4 side effects |  | 6 months | 
| Response to treatment of extra pulmonary localizations of the Langerhans disease |  | 6, 9, and 12 months | 
| Incidence of pneumothorax |  | 12 months | 
| Mortality |  | 12 months, 4 years | 
| Incidence of secondary malignant disease |  | 4 years | 
| Treatment response |  | at 6 months | 
| Treatment response |  | 9 months | 
| Treatment response |  | 12 months | 
| Variation of nodular and cystic semiquantitative scores in High Resolution Computed Tomography (HRCT) |  | 6 months |