Clinical Trial: Evaluation of Efficacy and Safety of Rituximab With Mycophenolate Mofetil in Patients With Interstitial Lung Diseases

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluation of Efficacy and Safety of Rituximab in Association With Mycophenolate Mofetil Versus Mycophenolate Mofetil Alone in Patients With Interstitial Lung Diseases (IL

Brief Summary: The purpose of the study is to evaluate the efficacy on lung function 6 months after one course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one course of placebo and 6 months of MMF treatment in a broad range of patients with Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.

Detailed Summary:
Sponsor: University Hospital, Tours

Current Primary Outcome: Change in FVC in % of predicted [ Time Frame: From baseline to 6 months ]

Change in FVC (in % of predicted) since declines in FVC correlates with increased risk of subsequent mortality in ILD patients and FVC is one of the core set of outcomes defined in interstitial lung diseases. Data obtained from the two groups of patients (rituximab and placebo) will be compared to each other. FVC will be performed in each study center in a standardized manner according to the ATS/ERS recommendations and ECCS reference equations


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Progression Free Survival (PFS). [ Time Frame: PFS measured at 3, 6 and 12 months ]
    PFS is defined as the time 1) to the first acute exacerbation, or 2) to an absolute decline of 10 % points in the percentage of the predicted FVC, or 3) to the necessity to withdraw the MMF with/without a new immunosuppressive treatment (except corticoids), or 4) to death or 5) registration to a lung transplantation list. An acute exacerbation is defined by (1) progressive dyspnea over 1 month or less; (2) new pulmonary infiltrates on chest radiography or computed tomography, and (3) the absence of an overt underlying cause of rapid deterioration
  • Changes in the quality of life score [ Time Frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough ]
    The quality of life score as measured by the SF-36 v1.3 questionnaire, version developed and validated in interstitial lung disease (ILD) patients.
  • Changes in the visual analogic scales of dyspnea [ Time Frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough ]
    Changes in the visual analogic scales of dyspnea (EVA test)
  • Cough evaluation [ Time Frame: Changes from baseline to 6 months in cough evaluation ]
    Changes in cough evaluation
  • Cumulative doses of corticoids for the 2 groups [ Time Frame: Cumulative doses of corticoids at 6 months ]
    Cumulative doses of corticoids for the 2 groups
  • Changes in the FVC expressed as % of predicted [ Time Frame: Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted ]
    Changes in the FVC expressed as % of predicted
  • Changes in DLCO [ Time Frame: Changes from baseline to 6 months in DLCO ]
    Changes in DLCO
  • Changes in the 6-minutes-walk test [ Time Frame: Changes from baseline to 6 months in the 6-minutes-walk test ]
    Changes in the 6-minutes-walk test
  • Changes in autoantibodies concentration [ Time Frame: Changes from baseline to 6 months in autoantibodies concentration ]
    Changes in autoantibodies concentration
  • Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes [ Time Frame: Changes from baseline to 6 months in lymphocytes B CD19 ]
    Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes
  • Changes in gammaglobulins [ Time Frame: Changes from baseline to 6 months in gammaglobulins ]
    Changes in gammaglobulins
  • Changes in HRCT of the chest images [ Time Frame: Changes from baseline to 6 months in HRCT of the chest images ]
    Changes in HRCT of the chest images
  • Adverse events related to treatment [ Time Frame: Adverse events during the 6 months of study period ]
    In particular infectious adverse events and biological blood disorders during the 6 months of study period will be collected
  • Rituximab PK parameters : distribution volume [ Time Frame: Points at Day1, Day15, 3 and 6 months ]
    Rituximab PK parameters : distribution volume
  • Rituximab clearance [ Time Frame: Points at Day1, Day15, 3 and 6 months ]
    Rituximab clearance
  • Half-life of rituximab in blood [ Time Frame: Points at Day1, Day15, 3 and 6 months ]
    Half-life of rituximab in blood


Original Secondary Outcome:

  • Progression Free Survival (PFS). [ Time Frame: PFS measured at 3, 6 and 12 months ]
    PFS is defined as the time 1) to the first acute exacerbation, or 2) to an absolute decline of 10 % points in the percentage of the predicted FVC, or 3) to the necessity to withdraw the MMF with/without a new immunosuppressive treatment (except corticoids), or 4) to death or 5) registration to a lung transplantation list. An acute exacerbation is defined by (1) progressive dyspnea over 1 month or less; (2) new pulmonary infiltrates on chest radiography or computed tomography, and (3) the absence of an overt underlying cause of rapid deterioration
  • Changes in the quality of life score [ Time Frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough ]
    The quality of life score as measured by the SF-36 v1.3 questionnaire, version developed and validated in interstitial lung disease (ILD) patients.
  • Changes in the visual analogic scales of dyspnea [ Time Frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough ]
    Changes in the visual analogic scales of dyspnea (EVA test)
  • Cough evaluation [ Time Frame: Changes from baseline to 6 months in cough evaluation ]
    Changes in cough evaluation
  • Cumulative doses of corticoids for the 2 groups [ Time Frame: Cumulative doses of corticoids at 6 months ]
  • Changes in the FVC expressed as % of predicted [ Time Frame: Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted ]
  • Changes in DLCO [ Time Frame: Changes from baseline to 6 months in DLCO ]
  • Changes in the 6-minutes-walk test [ Time Frame: Changes from baseline to 6 months in the 6-minutes-walk test ]
  • Changes in autoantibodies concentration [ Time Frame: Changes from baseline to 6 months in autoantibodies concentration ]
  • Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes [ Time Frame: Changes from baseline to 6 months in lymphocytes B CD19 ]
  • Changes in gammaglobulins [ Time Frame: Changes from baseline to 6 months in gammaglobulins ]
  • Changes in HRCT of the chest images [ Time Frame: Changes from baseline to 6 months in HRCT of the chest images ]
  • Adverse events related to treatment [ Time Frame: Adverse events during the 6 months of study period ]
    In particular infectious adverse events and biological blood disorders during the 6 months of study period will be collected
  • Rituximab PK parameters : distribution volume [ Time Frame: Points at Day1, Day15, 3 and 6 months ]
  • Rituximab clearance [ Time Frame: Points at Day1, Day15, 3 and 6 months ]
  • Half-life of rituximab in blood [ Time Frame: Points at Day1, Day15, 3 and 6 months ]


Information By: University Hospital, Tours

Dates:
Date Received: November 25, 2016
Date Started: January 20, 2017
Date Completion: January 2021
Last Updated: May 5, 2017
Last Verified: May 2017