Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD (RECITAL)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2013 by Royal Brompton & Harefield NHS Foundation Trust
Sponsor:
Collaborators:
Imperial College London
University of East Anglia
University College London Hospitals
Information provided by (Responsible Party):
Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01862926
First received: May 22, 2013
Last updated: May 24, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Interstitial Lung Disease
Scleroderma
Idiopathic Inflammatory Myositis
Mixed Connective Tissue Disease
Drug: Rituximab
Drug: Cyclophosphamide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Controlled Trial Comparing Rituximab Against Intravenous Cyclophosphamide in Connective Tissue Disease Associated Interstitial Lung Disease

Resource links provided by NLM:


Further study details as provided by Royal Brompton & Harefield NHS Foundation Trust:

Primary Outcome Measures:
  • Absolute change in FVC [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • • Change from baseline in diffusing capacity for carbon monoxide (DLco) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • • Change from baseline in health related quality of life scores [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • • Change from baseline in global disease activity score [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • • Progression free survival [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    composite endpoint of mortality, transplant, treatment failure or decline in FVC > 10% compared to baseline

  • • Adverse and serious adverse events (as defined in GCP) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 116
Study Start Date: June 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
1g given at baseline and two weeks.
Drug: Rituximab
Active Comparator: Cyclophosphamide
Intravenous dose of 600 mg/m2 body surface area. 6 doses given 4 weekly.
Drug: Cyclophosphamide

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 underlying connective 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 first presentation) and where there is a reasonable expectation that immunosuppressive treatment with stabilize or improve CTD-ILD. In individuals with scleroderma it is anticipated that subjects will fulfil the criteria for extensive disease defined by Goh et al19
  • Able to provide written informed consent

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 including cardiac, hepatic or renal impairment
  • Co-existent obstructive pulmonary disease (e.g. asthma, COPD, emphysema) with pre bronchodilator FEV1/FVC < 70%
  • Patients at significant risk for infectious complications following immunosuppression, including; HIV positive or other immunodeficiency syndromes (including hypogammaglobulineamia)
  • 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 mutifocal leukoencephalopathy; PML). Neurological symptoms arising as a consequence of the underlying CTD do not necessitate exclusion.
  • Other investigational therapy (participation in research trial) received within 8 weeks of visit 1
  • Immunosuppressive therapy (other than corticosteroids) received within 2 weeks of visit 1 (randomization)
  • Pregnant or breast feeding women, or women of child-bearing potential, not using a reliable contraceptive method
  • Unexplained haematuria, or previous bladder carcinoma
  • Unable to provide informed written consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01862926

Contacts
Contact: Toby M Maher, MD PhD 02073518018 t.maher@rbht.nhs.uk

Locations
United Kingdom
Royal Brompton Hospital Not yet recruiting
London, United Kingdom, SW3 6NP
Contact: Toby M Maher, MD PhD    0207 3518018    t.maher@rbht.nhs.uk   
Principal Investigator: Toby M Maher, MD PhD         
Sub-Investigator: Greg Keir, MD         
Sponsors and Collaborators
Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
University of East Anglia
University College London Hospitals
Investigators
Study Chair: Toby M Maher, MD PhD Royal Brompton and Harefield Foundation NHS Trust
  More Information

Additional Information:
Publications:

Responsible Party: Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01862926     History of Changes
Other Study ID Numbers: RBHIPF004, 2012-003633-42
Study First Received: May 22, 2013
Last Updated: May 24, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:
connective tissue disease
interstitial lung disease
pulmonary fibrosis
rituximab
scleroderma
polymyositis
dermatomyositis

Additional relevant MeSH terms:
Lung Diseases, Interstitial
Lung Diseases
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Mixed Connective Tissue Disease
Myositis
Respiratory Tract Diseases
Skin Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Cyclophosphamide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014