Rituximab in Interstitial Pneumonitis

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
rituximab	Zr-89-rituximab immuno PET/CT	single arm study with Zr-89-rituximab immuno PET/CT
rituximab	Rituximab	single arm study with Zr-89-rituximab immuno PET/CT

Primary Outcome Measures

Name	Time	Method
Pulmonary function (VC, DLCO)	6 - 12 months	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)

Secondary Outcome Measures

Name	Time	Method
Zr-89 Immuno PET	3, 6 days after injection	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.

Recruitment & Eligibility