Rituximab in Interstitial Pneumonitis

NCT02251964 | Completed Phase 2

• 2 other identifiers: NL49534.100.142013-005269-37
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Diseases, Interstitial; Pneumonitis, Interstitial

Keywords

IMID; Interstitial Pneumonitis; rituximab; Immuno PET; PET/CT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Zr-89 Immuno PET

  3, 6 days after injection

Study Arms (1)

rituximab

OTHER

single arm study with Zr-89-rituximab immuno PET/CT

Drug: Rituximab; Radiation: Zr-89-rituximab immuno PET/CT

Interventions

Rituximab DRUG

2 times 1000mg dose at 14 days interval treatment

rituximab

Zr-89-rituximab immuno PET/CT RADIATION

Immuno labeled PET/CT of the lungs

Also known as: Immuno PET

rituximab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Human Adams: lead
• Amsterdam UMC, location VUmc: collaborator

Study Sites (1)

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

Location

Related Publications (1)

• Adams H, van de Garde EMW, Vugts DJ, Grutters JC, Oyen WJG, Keijsers RG. [89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial. Eur J Nucl Med Mol Imaging. 2023 Jun;50(7):1929-1939. doi: 10.1007/s00259-023-06143-1. Epub 2023 Feb 24.

  PMID: 36826476 DERIVED

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Rituximab; Chromatin Immunoprecipitation Sequencing

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chromatin Immunoprecipitation; Genetic Techniques; Investigative Techniques; High-Throughput Nucleotide Sequencing; Sequence Analysis; Sequence Analysis, DNA; Immunoprecipitation; Immunologic Techniques

Study Officials

• J C Grutters, MD, PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. D.H. Biesma

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 29, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: February 1, 2018
• Last Updated: May 31, 2018

Record last verified: 2018-05

Locations

NL (1)