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

This study is currently recruiting participants.
Verified November 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01473797
First received: October 14, 2011
Last updated: November 19, 2012
Last verified: November 2012
History of Changes
  Purpose

ECLA is a phase II, single blinded, 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.


Condition Intervention Phase
Langerhans Cell Histiocytosis of Lung
 Drug: Cladribine
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Evaluation of Efficacy and Tolerance of Cladribine in Symptomatic Patients With Pulmonary Langerhans Cell Histiocytosis and Impairment of Lung Function

Resource links provided by NLM:

Drug Information available for: Cladribine
U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Cumulated incidence of response to treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Responses to treatment [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Absolute variations of FEV1, FVC, residual volume (RV), and Diffusing capacity of the lung for carbon monoxide (DLCO), (expressed in mL) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Grade 3 or 4 neutropenia or thrombopenia [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of infection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Incidence of grade 3 or 4 side effects [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Response to treatment of extra pulmonary localizations of the Langerhans disease [ Time Frame: 6, 9, and 12 months ] [ Designated as safety issue: No ]
  • Incidence of pneumothorax [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 12 months, 4 years ] [ Designated as safety issue: Yes ]
  • Incidence of secondary malignant disease [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Treatment response [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Treatment response [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • Treatment response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Variation of nodular and cystic semiquantitative scores in High Resolution Computed Tomography (HRCT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cladribine Drug: Cladribine
Subcutaneous injections, 0,1 mg/kg/day for 5 days, one course per month for 4 months
Other Name: Cladribine
Placebo Comparator: control Drug: Placebo
Subcutaneous injections of nacl 0.9% for 5 days, one course per month for 4 months
Other Name: Placebo

Detailed Description:

ECLA is a phase II, single blinded, 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.

For the purpose of efficacy analysis, patients will be stratified into two arms: placebo (NaCl 0.9%) versus cladribine.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01473797

Contacts
Contact: Abdellatif TAZI, MD, PhD 33(1) 42499618 abdellatif.tazi@sls.aphp.fr

Locations
France
Saint Louis hospital Recruiting
Paris, France, 75010
Contact: Abdellatif TAZI, MD, PhD     33(1)42499618     abdellatif.tazi@sls.aphp.fr    
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Abdellatif TAZI, MD, PhD AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01473797     History of Changes
Other Study ID Numbers: AOM10182, 2010-023344-32
Study First Received: October 14, 2011
Last Updated: November 19, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Histiocytosis
Histiocytosis, Langerhans-Cell
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Cladribine
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013