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Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 80 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT01862926
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2/Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Royal Brompton & Harefield NHS Foundation Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Toby M Maher, MD PhD
Principal Investigator Affiliation	Royal Brompton and Harefield Foundation NHS Trust
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Interstitial Lung Disease, Scleroderma, Idiopathic Inflammatory Myositis, Mixed Connective Tissue Disease

Arms & Interventions

Arms

Experimental: Rituximab

1g given at baseline and two weeks.

Active Comparator: Cyclophosphamide

Intravenous dose of 600 mg/m2 body surface area. 6 doses given 4 weekly.

Interventions

Drug: - Rituximab

Drug: - Cyclophosphamide

Contact a Trial Team

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