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 ]
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