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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Langerhans Cell Histiocytosis of Lung
• Intervention / Treatment: Drug: Cladribine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Saint Louis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 51 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	Time Frame
Incidence of infection	6 months
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 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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Abdellatif TAZI, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): April 1, 2018
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Histiocytosis, Langerhans-Cell; Histiocytosis; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cladribine
• Other Study ID Numbers: AOM10182; 2010-023344-32 (EudraCT Number)