The main objective of this study is to assess the effects of rituximab (RTX) as a rescue therapy for therapy resistant progressive IMID- IP patients. Specifically there is an objective assessment of (1) pulmonary function tests (PFTs) and (2)…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main objective of this study is to assess the effects of rituximab as a
rescue therapy for rare therapy resistant progressive IMID- IP patients. a) Our
primary goals can be measured by improvement of lung function in and
improvement in the quality of life (QoL).
Secondary outcome
Our secondary objectives are to assess potential predictors b) Parallel to the
treatment effect we will study additional parameters to potentially predict
treatment effect. The first consists of a unique rituximab scan to visualize
the potential binding sites for CD20 cells (and thus rituximab treatment
efficacy) and second, there are specific molecular markers assessed by blood
analysis which may give additional insight in the disease. Additional
objectives are to assess the cost burden of the disease: c) Cost effectiveness:
these consist of the cost savings when preventing or delaying lung transplants
vs. the cost of rituximab, improvement in lung function and quality of life.
Background summary
Immune mediated inflammatory diseases (IMIDs) encompass a broad spectrum of
inflammatory disorders and this project will address rare IMIDs involving the
lungs. When left untreated, interstitial pneumonitis (IP) can lead to poor
quality of life due to worsening of the pulmonary function, ultimately leading
to an increased mortality. Due to the extreme rarity of the condition, known as
IMID-IP, no large randomized trial can ever be performed. Current treatments of
this disease are with various immunosuppressive drugs, however unfortunately
not all patients respond. Those with advancing IP will ultimately risk
respiratory failure and death. Even though lung transplantation could be a
final option, this is a rare and extremely expensive procedure. Thus there is a
strong demand for a new therapeutic option. Recent studies on immune mediated
diseases in rheumatology and also lung inflammatory disease show encouraging
results with rituximab. A clinical improvement as well as improvement of lung
function has been demonstrated in a number of cases. Since rituximab
effectively suppresses CD20 B lymphocytes, this gives rise to fundamental
questions of the role of CD20 in inflammation. Since the study population is so
rare, only an experienced and specialized tertiary referral center may provide
the necessary conditions for a phase III trial with rituximab. When rituximab
can stabilize disease and improve lung function this could provide the patient
with a new life saving treatment option. In addition, delay or prevention of
lung transplantation has significant potential for cost savings.
Study objective
The main objective of this study is to assess the effects of rituximab (RTX) as
a rescue therapy for therapy resistant progressive IMID- IP patients.
Specifically there is an objective assessment of (1) pulmonary function tests
(PFTs) and (2) Quality of Life measurement The secondary objectives are to
assess the value of (1) an innovative rituximab scan to visualize RTX target
sites (2) various prognostic markers biomarkers (3) cost effectiveness of the
RTX treatment
Study design
Prospective study following an interrupted time series (ITS) design.
Study burden and risks
Since there are currently no other options to treat immune mediated pulmonary
inflammation, apart from waiting in the lung transplant list, the offlabel
treatment with rituximab seems justifiable. Serious side effects may occur,
however these are extremely rare. Furthermore we are the first study to utilize
a Zr-89 immuno PET/CT scan (rituximab scan) to analyse possible patient
characteristics of responders and non-responders. This is very useful in this
rare disease population for future patients. This way it may become possible in
the future to select patients accordingly on the basis of chances of reponse,
and thereby avoiding unnecessary treatments in non-responders.
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Listed location countries
Age
Inclusion criteria
• Age: 18 - 70 years • No previous therapy with rituximab • Diagnosis of co-existing IMID and a severe and / or progressive IP by one of the following: - Clinical symptoms consistent with interstitial lung disease between 3 months and 3 years prior to screening - FVC <50% pred. and/or DLCO <40% pred. - 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 - HRCT scan showing definite or probable UIP / NSIP / OP / mixed - Worsening 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 (cyclophosamide, AZT) • At least 2x PFT measurements in last 6 months
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 • 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. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005269-37-NL |
| CCMO | NL49534.100.14 |