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Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease (SCLEROCYC)

This study is currently recruiting participants.
Verified August 2016 by Assistance Publique - Hôpitaux de Paris
Sponsor:
ClinicalTrials.gov Identifier:
NCT01570764
First Posted: April 4, 2012
Last Update Posted: September 15, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Hôpital Claude-Huriez
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose
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.

Condition Intervention Phase
Systemic Sclerosis Scleroderma Interstitial Lung Disease Lung Fibrosis Drug: Cyclophosphamide Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intravenous Cyclophosphamide for the Treatment of Systemic Sclerosis Associated Interstitial Lung Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Forced vital capacity [ Time Frame: at 12 months ]
    Forced vital capacity at 12 months


Secondary Outcome Measures:
  • Mortality [ Time Frame: at 12 months ]
  • Progression free survival [ Time Frame: at 12 months ]
    Progression free survival

  • Carbon monoxide diffusing capacity (DLCO) [ Time Frame: at 12 months ]
  • Treatment failure [ Time Frame: at 12 months ]
    Failure of cyclophosphamide or placebo

  • Walk test distance [ Time Frame: at 12 months ]
    Six minutes walk test distance, O2 desaturation and gradient between maximal and minimal SAO2 during the test

  • Dyspnea [ Time Frame: at 12 months ]
    NYHA (Classification de la New York Heart Association), BDI (Beck Depression Inventory) and Borg index

  • Health Assessment Questionnaire [ Time Frame: at 12 months ]
  • Quality of life [ Time Frame: at 12 months ]
    Saint-Georges; SF-36

  • Chest CT (computed tomography) scan [ Time Frame: at 12 months ]
    CT (computed tomography) scan abnormalities


Estimated Enrollment: 50
Study Start Date: January 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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
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

Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 3 to 18 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.
  • 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 ...)
  • Patients with a past history of cancer within four years before inclusion and/or a history of chemotherapy for cancer within four years before inclusion (in remission or without disease activity for more than four 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01570764


Contacts
Contact: Luc Mouthon, MD, PhD ++33158412031 luc.mouthon@cch.aphp.fr
Contact: Laurence Lecomte, PhD ++33171196474 laurence.lecomte@nck.aphp.fr

Locations
France
Cochin Hospital Recruiting
Paris, France, 75014
Contact: Luc Mouthon, MD, PhD    ++33158412031    luc.mouthon@cch.aphp.fr   
Principal Investigator: Luc Mouthon, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Hôpital Claude-Huriez
Investigators
Principal Investigator: Luc Mouthon, MD, PhD Cochin Hospital
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01570764     History of Changes
Other Study ID Numbers: P081241
2011-004709-26 ( EudraCT Number )
First Submitted: April 2, 2012
First Posted: April 4, 2012
Last Update Posted: September 15, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Systemic sclerosis
Interstitial lung disease
Worsening
Cyclophosphamide
Intravenous

Additional relevant MeSH terms:
Lung Diseases, Interstitial
Sclerosis
Lung Diseases
Scleroderma, Systemic
Scleroderma, Diffuse
Pulmonary Fibrosis
Pathologic Processes
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Cyclophosphamide
Prednisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal