Whole Lung Lavage (WLL)/Inhaled Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (PAP)
|ClinicalTrials.gov Identifier: NCT00901511|
Recruitment Status : Unknown
Verified July 2009 by IRCCS Policlinico S. Matteo.
Recruitment status was: Enrolling by invitation
First Posted : May 13, 2009
Last Update Posted : July 28, 2009
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Alveolar Proteinosis||Drug: GM-CSF [Leukine (Sargramostim)] Procedure: WLL||Phase 2 Phase 3|
Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by accumulation of lipoproteinaceous material within alveolar spaces, leading to respiratory failure. Whole lung lavage (WLL) is the current therapeutic option, but it may induce complete resolution of the disorder only in 30% of patients. Based on PAP pathophysiology, a few pilot studies dealing with administration of rGM-CSF (Sargramostim) to patients either s.c. or aerosolized have been performed, with hopeful results.Objectives. We designed an experimental, randomized by parallel groups, stratified according to previous treatment, open-label study looking at evaluation the superiority of the combination WLL/inhaled GM-CSF vs WLL alone in PAP patients. The study also includes a side, observational section. The primary efficacy objective is the total resolution of the pulmonary involvement in all treated patients. The study includes some secondary efficacy objectives as well: avoidance of disease recurrence, avoidance of respiratory infections, investigation of biomarkers predicting the disease outcome, effect of treatments on underlying pathophysiology of PAP.
PAP patients matching the enrollment criteria will enter the study. 1) If requiring the first WLL, they will be randomized to receive WLL (1st level control group) or WLL/ followed by inhaled GM-CSF, according to an acute (12 weeks) followed by maintenance (6 months) schedule (1st level treated group). 2) PAP patients requiring the second WLL: a) the 1st level control group subjects will be randomized to receive WLL alone (2nd level control group) or WLL/GM-CSF (2nd level treated group); b) the 1st level treated group will receive WLL/GM-CSF (1st level re-treated group). 3) PAP patients requiring the 3rd WLL will receive WLL/GM-CSF (2nd level re-treated group). 4) PAP patients not requiring additional WLL, but with persistent lung abnormalities will receive the course of inhaled GM-CSF (Residual disease treated group). At scheduled time, the PAP patients will be evaluated by questionnaire, respiratory function testing, CT-assisted lung profusion score, severity score, quality of life form, clinical chemistry.
We plan to identify the best treatment schedule for PAP patients. We will be able to identify the optimal sequence of the treatments (i.e., WLL + short-term inhaled GM-CSF or WLL + short-and long-term inhaled GM-CSF) and the optimal treatment in case of recurrence.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Whole Lung Lavage Followed by Inhaled Sargramostim in the Treatment of Autoimmune Pulmonary Alveolar Proteinosis|
|Study Start Date :||July 2009|
|Estimated Primary Completion Date :||July 2012|
|Estimated Study Completion Date :||July 2013|
Whole lung lavage followed by inhaled GM-CSF
Drug: GM-CSF [Leukine (Sargramostim)]
Acute treatment: the PAP subjects will receive inhaled rGM-CSF (Sargramostim, Leukine) at the dose of 250 mcg/24 hours. The acute treatment will be accomplished in 12 weeks, for 7 consecutive days every second week (thus, 6 weeks on and 6 weeks off). For those PAP patients receiving the GM-CSF for the first time (1st and 2nd level treated groups), the treatment will be performed by 1 week run-in, after discharge from the ICU, in the Respiratory Disease Department (during this period PAP patients usually receive e.v. corticosteroids, and oral antibiotics). After the run-in period, the patient is discharged and inhalation treatment will continue at home.
Maintenance treatment: 17 weeks after the WLL (4 weeks after the completion of the acute treatment), the PAP patient will start the maintenance treatment. He/she will receive inhaled GM-CSF at the dose of 250 mcg/daily for 2 consecutive days every 14 days (2 days on and 12 days off) for a period of 6 month
Other Name: Leukine (Sargramostim)Procedure: WLL
Whole lung lavage
|Active Comparator: WLL alone||
Whole lung lavage
- The total resolution of the pulmonary involvement [ Time Frame: 36 months ]
- Avoidance of recurrence of the disease requiring multiple WLLs [ Time Frame: 36 months ]
- Investigation of determinants of the outcome [ Time Frame: 36 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00901511
|Fondazione IRCCS Policlinico San Matteo|
|Pavia, PV, Italy, 27100|
|Principal Investigator:||Maurizio Luisetti, MD||Fondazione IRCCS Policlinico San Matteo|