Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease

Systemic Sclerosis Clinical Trial

— SCLEROCYC  

Official title:

Intravenous Cyclophosphamide for the Treatment of Systemic Sclerosis Associated Interstitial Lung Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01570764
• Other study ID #: P081241
• Secondary ID: 2011-004709-26
• Status: Completed
• Phase: Phase 3
• Start date: January 14, 2013
• Est. completion date: February 22, 2018

Study information

• Verified date: November 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

By including in this study patients with significant worsening of their lung volumes and / or their DLCO (carbon monoxide diffusing capacity) in the previous year, on the basis of an open retrospective study we recently conducted, we hope to demonstrate that a strategy combining prednisone and intravenous cyclophosphamide therapy is accompanied by an increase in the frequency stabilization / improvement of lung volumes and / or DLCO of patients at 12 months of 15% in the placebo and prednisone cyclophosphamide 50% in cyclophosphamide and prednisone.We also hope to demonstrate significant decrease in the number of patients excluded for failure in the CYC arm as compared to the placebo arm.

Description:

This is a randomized prospective multicenter study evaluating the efficacy against placebo of cyclophosphamide in combination with prednisone in the treatment of systemic sclerosis related interstitial lung disease. Patients will be allocated, after randomization into two groups receiving both corticosteroids: a group of patients receiving placebo of cyclophosphamide and a group of patients treated with cyclophosphamide. Cyclophosphamide will be administered IV at a dose of 0.7 g / m (maximum 1200 mg) every 4 weeks. In patients over 65 or if the creatinine clearance below 30 ml / min the dose should be reduced to 0.6 g / m². The duration of treatment with cyclophosphamide will be 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 22, 2018
• Est. primary completion date: February 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years old

• Signed informed consent

• Patient with systemic sclerosis fulfilling the ACR -American college of rheumatology - (Masi et al. 1980) and/or Leroy and Medsger (LeRoy and Medsger 2001) diagnostics criteria with worsening ILD (interstitial lung disease) identified on a high resolution chest CT scan and by worsening of forced vital capacity (FVC) and/or total lung capacity (TLC) =10% and/or worsening of DLCO = 15% as compared to values obtained within the 3 to 18 months preceding inclusion (for DLCO, in the absence of pulmonary arterial hypertension upon echocardiography)

• Smokers may be included (DLCO must be performed at least 72h after stopping tobacco intake).

• Patients with pulmonary hypertension (mean pulmonary arterial pressure <35 mmHg upon right heart catheterisation) secondary to hypoxia due to pulmonary fibrosis will also be included into the study.

• Physical examination prior to inclusion into the study (results must be given to the patient).

-: Contraception considered effective by the investigator (abstinence and / or oral contraception or mechanical) for women of childbearing age (negative pregnancy test at baseline)

• Affiliation with a mode of social security (profit or being entitled)

Exclusion Criteria:

• Prednisone prescribed a dose greater than 15 mg/d during the last 3 months.

• Scleroderma renal crisis or acute or critical limb ischemia within the last year preceding inclusion,

• Left ventricular ejection fraction below 40% evaluated by echocardiography.

• Out of proportion pulmonary hypertension (mean pulmonary artery pressure above 35 mmHg upon right heart catheterization).

• CYC treatment during the last 12 months.

• Allergy, hypersensitivity or documented adverse events or contra-indications to the drugs used in the study (cyclophosphamide, Uromitexan, corticosteroids, domperidone ...)

• Patients with a past history of cancer within four years before inclusion and/or a history of chemotherapy for cancer within four years before inclusion (in remission or without disease activity for more than four years). Inclusion is authorized for patients with a basal cell carcinoma in the last 5 years.

• Severe infection: sepsis, cellulitis, gangrene in the last three months

• Past history of cystitis related to cyclophosphamide treatment

• Association to another connective disease : systemic lupus erythematosus, syndrome of Gougerot-Sjögren with anti-SSA/SSB, mixed connective tissue disease

• Patient breastfeeding

• Failure to sign the informed consent or unable to consent

• Patient participating in another clinical trial

• Injection of Rituximab within 6 months preceding inclusion

• Methotrexate or Cellcept treatment at inclusion

Related Conditions & MeSH terms

• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Lung Fibrosis
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Cyclophosphamide
Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.
• Placebo
Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide

Locations

Country	Name	City	State
France	Cochin Hospital	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Hôpital Claude-Huriez

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced vital capacity	Forced vital capacity at 12 months	at 12 months
Secondary	Mortality		at 12 months
Secondary	Progression free survival	Progression free survival	at 12 months
Secondary	Carbon monoxide diffusing capacity (DLCO)		at 12 months
Secondary	Treatment failure	Failure of cyclophosphamide or placebo	at 12 months
Secondary	Walk test distance	Six minutes walk test distance, O2 desaturation and gradient between maximal and minimal SAO2 during the test	at 12 months
Secondary	Dyspnea	NYHA (Classification de la New York Heart Association), BDI (Beck Depression Inventory) and Borg index	at 12 months
Secondary	Health Assessment Questionnaire		at 12 months
Secondary	Quality of life	Saint-Georges; SF-36	at 12 months
Secondary	Chest CT (computed tomography) scan	CT (computed tomography) scan abnormalities	at 12 months