Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease (SCLEROCYC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
Service de Médecine Interne de l'hôpital Claude-Huriez, Lille, France - Pr David Launay
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01570764
First received: April 2, 2012
Last updated: January 2, 2014
Last verified: January 2014

April 2, 2012
January 2, 2014
January 2013
January 2016   (final data collection date for primary outcome measure)
Forced vital capacity [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
Forced vital capacity at 12 months
Forced vital capacity [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
To increase the proportion of patients improved or stabilized on forced vital capacity at 12 months from 15 % in the arm placebo of CYC (cyclophosphamide) + prednisone to 50 % in the arm CYC + prednisone.
Complete list of historical versions of study NCT01570764 on ClinicalTrials.gov Archive Site
  • Mortality [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • Progression free survival [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
    Progression free survival
  • Carbon monoxide diffusing capacity (DLCO) [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • Treatment failure [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
    Failure of cyclophosphamide or placebo
  • Walk test distance [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Six minutes walk test distance, O2 desaturation and gradient between maximal and minimal SAO2 during the test
  • Dyspnea [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    NYHA (Classification de la New York Heart Association), BDI (Beck Depression Inventory) and Borg index
  • Health Assessment Questionnaire [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Saint-Georges; SF-36
  • Chest CT (computed tomography) scan [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    CT (computed tomography) scan abnormalities
  • Decreased mortality [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • Free survival [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
    To increase in progression free survival
  • Carbon monoxide diffusing capacity (DLCO) [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
    Increase from 15 % to 50 % of the proportion of patients improved or stabilized at 12 months on DLCO in the CYC + prednisone arm as compared to the placebo of CYC + prednisone arm.
  • Failure in the cyclophosphamide arm [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
    Significant decrease in the number of patients excluded for failure in the CYC arm as compared to the placebo arm
  • Walk test distance [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Modification of the six minutes walk test distance, O2 desaturation and gradient between maximal and minimal SAO2 during the test
  • Dyspnea [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Improvement if dyspnea as assessed by the NYHA (Classification de la New York Heart Association), BDI (Beck Depression Inventory) and Borg index
  • Health Assessment Questionnaire [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Improvement of Health Assessment Questionnaire disability index (HAQ-DI)
  • Quality of life [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Improvement of a quality of life scale (Saint-Georges/SF-36)
  • Chest CT (computed tomography) scan [ Time Frame: at 12 months ] [ Designated as safety issue: No ]
    Improvement of chest CT (computed tomography) scan abnormalities
Not Provided
Not Provided
 
Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
Intravenous Cyclophosphamide for the Treatment of Systemic Sclerosis Associated Interstitial Lung Disease

By including in this study patients with significant worsening of their lung volumes and / or their DLCO (carbon monoxide diffusing capacity) in the previous year, on the basis of an open retrospective study we recently conducted, we hope to demonstrate that a strategy combining prednisone and intravenous cyclophosphamide therapy is accompanied by an increase in the frequency stabilization / improvement of lung volumes and / or DLCO of patients at 12 months of 15% in the placebo and prednisone cyclophosphamide 50% in cyclophosphamide and prednisone.We also hope to demonstrate significant decrease in the number of patients excluded for failure in the CYC arm as compared to the placebo arm.

This is a randomized prospective multicenter study evaluating the efficacy against placebo of cyclophosphamide in combination with prednisone in the treatment of systemic sclerosis related interstitial lung disease. Patients will be allocated, after randomization into two groups receiving both corticosteroids: a group of patients receiving placebo of cyclophosphamide and a group of patients treated with cyclophosphamide. Cyclophosphamide will be administered IV at a dose of 0.7 g / m (maximum 1200 mg) every 4 weeks. In patients over 65 or if the creatinine clearance below 30 ml / min the dose should be reduced to 0.6 g / m². The duration of treatment with cyclophosphamide will be 12 months.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Systemic Sclerosis
  • Scleroderma
  • Interstitial Lung Disease
  • Lung Fibrosis
  • Drug: Cyclophosphamide
    Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.
  • Drug: Placebo
    Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide
  • Experimental: Cyclophosphamide
    Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.
    Intervention: Drug: Cyclophosphamide
  • Placebo Comparator: Placebo
    Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
84
July 2016
January 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age ≥ 18 years old
  • Signed informed consent
  • Patient with systemic sclerosis fulfilling the ACR -American college of rheumatology - (Masi et al. 1980) and/or Leroy and Medsger (LeRoy and Medsger 2001) diagnostics criteria with worsening ILD (interstitial lung disease) identified on a high resolution chest CT scan and by worsening of forced vital capacity (FVC) and/or total lung capacity (TLC) ≥10% and/or worsening of DLCO ≥ 15% as compared to values obtained within the 12±6 months preceding inclusion (for DLCO, in the absence of pulmonary arterial hypertension upon echocardiography)
  • Smokers may be included (DLCO must be performed at least 72h after stopping tobacco intake).
  • Patients with pulmonary hypertension (mean pulmonary arterial pressure <35 mmHg upon right heart catheterisation) secondary to hypoxia due to pulmonary fibrosis will also be included into the study.
  • Physical examination prior to inclusion into the study (results must be given to the patient).
  • Effective contraception for women of childbearing age(negative pregnancy test at baseline)
  • Membership of a social security scheme

Exclusion Criteria:

  • Prednisone prescribed a dose greater than 15 mg/d during the last 3 months.
  • Anti-fibrotic treatment prescribed during the study period (except the D-penicillamine which is allowed if it is prescribed for more than three months at the time of inclusion stable dose).
  • Scleroderma renal crisis or acute or critical limb ischemia within the last 3 months,
  • Left ventricular ejection fraction below 40% evaluated by echocardiography.
  • Out of proportion pulmonary hypertension (mean pulmonary artery pressure above 35 mmHg upon right heart catheterization).
  • CYC treatment during the last 12 months.
  • Allergy, hypersensitivity or documented adverse events or contra-indications to the drugs used in the study (cyclophosphamide, Uromitexan, corticosteroids, domperidone ...)
  • Chemotherapy for cancer within 5 years preceding inclusion.
  • Cancer in the previous five years (remission or no scalability for over 5 years)
  • Severe infection: sepsis, cellulitis, gangrene in the last three months
  • Past history of cystitis related to cyclophosphamide treatment
  • Association to another connective disease : systemic lupus erythematosus, syndrome of Gougerot-Sjögren with anti-SSA/SSB, mixed connective tissue disease
  • Patient pregnant, lactating or not using contraception considered effective by the investigator (abstinence and / or oral contraception or mechanical)
  • Patient in childbearing, refusing contraception
  • Failure to sign the informed consent or unable to consent-Patient participating in another clinical trial
  • Injection of Rituximab within 6 months preceding inclusion
  • Methotrexate or Cellcept treatment at inclusion
Both
18 Years and older
No
Contact: Luc Mouthon, MD, PhD ++33158412031 luc.mouthon@cch.aphp.fr
Contact: Laurence Lecomte, PhD ++33171196474 laurence.lecomte@nck.aphp.fr
France
 
NCT01570764
P081241, 2011-004709-26
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Service de Médecine Interne de l'hôpital Claude-Huriez, Lille, France - Pr David Launay
Principal Investigator: Luc Mouthon, MD, PhD Cochin Hospital
Assistance Publique - Hôpitaux de Paris
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP