Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD

Last updated: October 6, 2021
Sponsor: Royal Brompton & Harefield NHS Foundation Trust
Overall Status: Completed

Phase

2/3

Condition

Dermatomyositis (Connective Tissue Disease)

Musculoskeletal Diseases

Lupus

Treatment

N/A

Clinical Study ID

NCT01862926
RBHIPF004
2012-003633-42
  • Ages 18-80
  • All Genders

Study Summary

Interstitial lung disease (ILD) is characterised by inflammation and scarring of the lung and is the leading cause of death in patients with systemic sclerosis, and contributes significantly to morbidity and mortality in many other connective tissue diseases (CTDs) such as polymyositis/dermatomyositis and mixed connective tissue disease. When ILD is extensive and/or progressive, immunosuppressive medication is often required to stabilize lung disease and alleviate symptoms. Current standard care for CTD associated ILD is extrapolated from studies performed in individuals with systemic sclerosis and comprises low dose corticosteroids and intravenous cyclophosphamide followed by oral azathioprine. In some individuals even this intensive immunosuppression is insufficient to prevent deterioration, and in a significant minority of affected individuals this results in respiratory failure and death. Rituximab has recently been reported as an effective 'rescue therapy' for stabilizing and even improving ILD in this patient group. Based on observations gained from this experience, the investigators believe that rituximab is a potential important alternative to current best therapy for this patient group. This study has therefore been initiated to evaluate the efficacy of rituximab (compared with standard therapy) in patients with progressive CTD related ILD.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age 18 to 80 years at visit 1
  • A diagnosis of connective tissue disease, based on internationally accepted criteria,in one of the following categories21-24: (see Appendix 1 for details)
  • Systemic sclerosis
  • Idiopathic interstitial myopathy (including polymyositis/dermatomyositis)
  • Mixed connective tissue disease
  • Severe and/or progressive interstitial lung disease associated with the underlyingconnective tissue disease.
  • Chest HRCT performed within 12 months of study visit 1
  • Intention of the caring physician to treat the ILD with intravenous cyclophosphamide (with treatment indications including deteriorating symptoms attributable to ILD,deteriorating lung function tests, worsening gas exchange or extent of ILD at firstpresentation) and where there is a reasonable expectation that immunosuppressivetreatment with stabilize or improve CTD-ILD. In individuals with scleroderma it isanticipated that subjects will fulfil the criteria for extensive disease defined byGoh et al19
  • Able to provide written informed consent

Exclusion

Exclusion Criteria:

  • Age <18 or >80 years.
  • Previous treatment with rituximab and/or intravenous cyclophosphamide
  • Known hypersensitivity to rituximab or cyclophosphamide or their components
  • Significant (in the opinion of the investigator) other organ co-morbidity includingcardiac, hepatic or renal impairment
  • Co-existent obstructive pulmonary disease (e.g. asthma, COPD, emphysema) with prebronchodilator FEV1/FVC < 70%
  • Patients at significant risk for infectious complications following immunosuppression,including; HIV positive or other immunodeficiency syndromes (includinghypogammaglobulineamia)
  • Suspected or proven untreated tuberculosis
  • Viral hepatitis
  • Infection requiring antibiotic treatment in the preceding four weeks
  • Unexplained neurological symptoms (which may be suggestive of progressive mutifocalleukoencephalopathy; PML). Neurological symptoms arising as a consequence of theunderlying CTD do not necessitate exclusion.
  • Other investigational therapy (participation in research trial) received within 8weeks of visit 1
  • Immunosuppressive therapy (other than corticosteroids) received within 2 weeks ofvisit 1 (randomization)
  • Pregnant or breast feeding women, or women of child-bearing potential, not using areliable contraceptive method
  • Unexplained haematuria, or previous bladder carcinoma
  • Unable to provide informed written consent

Study Design

Total Participants: 104
Study Start date:
November 01, 2014
Estimated Completion Date:
January 31, 2021

Connect with a study center

  • Royal Brompton Hospital

    London, SW3 6NP
    United Kingdom

    Site Not Available

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