Rituximab in Interstitial Pneumonitis

Study Overview
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Brief Summary
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This project will address rare immune mediated inflammatory diseases (IMIDs) involving the lungs, i.e. interstitial pneumonitis (IP). The main objective of this study is to assess the effects of rituximab (RTX) as a rescue therapy for progressive IMID-IP patients. The primary study parameter is pulmonary function. The secondary objectives are to explore the application of imaging with radiolabeled RTX as early predictor for efficacy of RTX, to study the effects of RTX treatment on quality of life, and to further elucidate the pathophysiology of IMID-IP by analyzing biochemical markers.

Official Title
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Rituximab in Life Threatening Therapy Resistant Progressive Interstitial Pneumonitis

Conditions
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Lung Diseases, Interstitial, Pneumonitis, Interstitial

Intervention / Treatment
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* Drug: Rituximab
* Radiation: Zr-89-rituximab immuno PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in the study, subjects must meet all of the following criteria: Age 18 to 70 years No previous therapy with rituximab At least 2 pulmonary function tests within past 6 months Diagnosis of co-existing IMID and a severe and / or progressive IP characterized by 3 out of the following items: Respiratory symptoms consistent with interstitial lung disease Diagnosis of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) or a mixed form of UIP / NSIP / OP by either of the following: Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or probable UIP / NSIP / OP High Resolution Computer Tomography (HRCT) scan showing definite or probable UIP/NSIP/OP/mixed Forced Vital Capacity (FVC) < 50% predicted and/or diffusing capacity of the lung for carbon monoxide (DLCO) < 40% predicted or worsening of lung function as demonstrated by any one of the following within the past year: > 10% decrease in FVC > 15% decrease in DLCO Therapy resistance to 1st (corticosteroids) and 2nd line therapy(cyclophosphamide or azathioprine) Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: Residual volume >120% predicted at screening DLCO <25% of predicted value at screening + resting Oxygen Saturation (SAO2) without external oxygen <90% History of unstable or deteriorating cardiac or neurological disease Pregnancy or lactation Hematology lower than specified limits (leucocytes) Positive HIV, hepatitis B or C serology Pre-existing conditions which lead to a life expectancy of less than 6 months Receipt of any vaccine, particularly live viral vaccines, within 4 weeks before first rituximab dose Hypersensitivity for murine proteins NOTE: Fever (>37,9 °C) at presentation is reason to delay therapy by 1 week Evidence of active infection is reason to postpone rituximab treatment until no further signs of active infection Severe renal impairment is not a contraindication for rituximab therapy, however, if patients (might) require dialysis frequently they will be excluded from the study group

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: rituximab<br>single arm study with Zr-89-rituximab immuno PET/CT | Drug: Rituximab<br>* 2 times 1000mg dose at 14 days interval treatment<br>Radiation: Zr-89-rituximab immuno PET/CT<br>* Immuno labeled PET/CT of the lungs<br>* Other names: Immuno PET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function (VC, DLCO) | establish a change from the downward decline in pulmonary function (absolute values and values predicted of VC = Vital Capacity and DLCO = Diffusion capacity of Lung Carbon monoxide) | 6 - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zr-89 Immuno PET | This is a scan with radiolabelled rituximab (visualizing rituximab activity in the lungs). Calculated activity (SUV) in the lungs vs. blood pool vs liver vs.control group (n=15) is measured with standard deviation. The amount of uptake in the lungs and the clinical response of patients will be correlated to determine a correlation. | 3, 6 days after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interstitial Pneumonitis, rituximab, Immuno PET, IMID, PET/CT