NCT00004563

Brief Summary

To evaluate the efficacy and safety of cyclophosphamide versus placebo for the prevention and progression of symptomatic pulmonary disease in patients with systemic sclerosis.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
158

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Aug 1999

Longer than P75 for phase_3

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 1999

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 9, 2000

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 10, 2000

Completed
13.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

March 6, 2015

Completed
Last Updated

March 27, 2015

Status Verified

March 1, 2015

Enrollment Period

13.8 years

First QC Date

February 9, 2000

Results QC Date

February 19, 2015

Last Update Submit

March 5, 2015

Conditions

Lung DiseasesPulmonary FibrosisSystemic SclerodermaScleroderma, Systemic

Keywords

Lung DiseasesPulmonary FibrosisSystemic SclerodermaScleroderma, systemic

Outcome Measures

Primary Outcomes (1)

  • Forced Vital Capacity

    The primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.

    12 months

Secondary Outcomes (2)

  • Total Lung Capacity

    12 months

  • DLCO

    12 months

Study Arms (2)

Cylophosphamide

EXPERIMENTAL

Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.

Drug: Cyclophosphamide

Placebo

PLACEBO COMPARATOR

Matching gel caps at a dose of 25 mg

Drug: Placebo

Interventions

CyclophosphamideDRUG

Cyclophosphamide (Cytoxan, Bristol-Myers Squibb) was initiated with a dose of 1 mg per kilogram of body weight per day (to the nearest 25 mg). The doses were increased monthly by one capsule up to 2 mg per kilogram.

Also known as: Cytoxan (Bristol Myers Squibb)
Cylophosphamide
PlaceboDRUG

Matching gelcaps 25 mgs

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with limited or diffuse systemic scleroderma if they had evidence of active alveolitis on examination of bronchoalveolar-lavage (BAL) fluid (defined as neutrophilia of ≥3 percent, eosinophilia of ≥2 percent, or both)on thoracic high-resolution computed tomography (CT), any ground-glass opacity,
  • Onset of the first symptom of scleroderma other than Raynaud's phenomenon within the previous seven years,
  • An FVC between 45 and 85 percent of the predicted value
  • Grade 2 exertional dyspnea according to the baseline instrument of the Mahler Dyspnea Index (as measured with the use of the magnitude-of-task component).

You may not qualify if:

  • A single-breath carbon monoxide diffusing capacity (DlCO) that was less than 30 percent of the predicted value,
  • A history of smoking within the preceding six months, other clinically significant pulmonary abnormalities,
  • Clinically significant pulmonary hypertension requiring drug therapy.
  • Patients taking prednisone at a dose of more than 10 mg per day, those who had previously been treated for more than four weeks with oral cyclophosphamide or had received two or more intravenous doses,
  • Patients who recently received other potentially disease-modifying medications.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (14)

  • Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M; Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006 Jun 22;354(25):2655-66. doi: 10.1056/NEJMoa055120.

    PMID: 16790698RESULT

  • Volkmann ER, Wilhalme H, Good S, Kim GHJ, Goldin J, Roth MD, Tashkin DP. A composite endpoint for systemic sclerosis-associated interstitial lung disease: association with mortality in two clinical trial cohorts. Respir Res. 2025 Nov 28;26(1):337. doi: 10.1186/s12931-025-03401-8.

    PMID: 41316297DERIVED

  • Khanna D, Clements PJ, Volkmann ER, Wilhalme H, Tseng CH, Furst DE, Roth MD, Distler O, Tashkin DP. Minimal Clinically Important Differences for the Modified Rodnan Skin Score: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Arthritis Res Ther. 2019 Jan 16;21(1):23. doi: 10.1186/s13075-019-1809-y.

    PMID: 30651141DERIVED

  • Kafaja S, Clements PJ, Wilhalme H, Tseng CH, Furst DE, Kim GH, Goldin J, Volkmann ER, Roth MD, Tashkin DP, Khanna D. Reliability and minimal clinically important differences of forced vital capacity: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Am J Respir Crit Care Med. 2018 Mar 1;197(5):644-652. doi: 10.1164/rccm.201709-1845OC. Epub 2017 Nov 3.

    PMID: 29099620DERIVED

  • Namas R, Tashkin DP, Furst DE, Wilhalme H, Tseng CH, Roth MD, Kafaja S, Volkmann E, Clements PJ, Khanna D; Participants in the Scleroderma Lung Study I and members of the Scleroderma Lung Study II Research Group. Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2018 Mar;70(3):439-444. doi: 10.1002/acr.23282. Epub 2018 Feb 9.

    PMID: 28544580DERIVED

  • Kim HJ, Tashkin DP, Gjertson DW, Brown MS, Kleerup E, Chong S, Belperio JA, Roth MD, Abtin F, Elashoff R, Tseng CH, Khanna D, Goldin JG. Transitions to different patterns of interstitial lung disease in scleroderma with and without treatment. Ann Rheum Dis. 2016 Jul;75(7):1367-71. doi: 10.1136/annrheumdis-2015-208929. Epub 2016 Jan 12.

    PMID: 26757749DERIVED

  • Khanna D, Nagaraja V, Tseng CH, Abtin F, Suh R, Kim G, Wells A, Furst DE, Clements PJ, Roth MD, Tashkin DP, Goldin J. Predictors of lung function decline in scleroderma-related interstitial lung disease based on high-resolution computed tomography: implications for cohort enrichment in systemic sclerosis-associated interstitial lung disease trials. Arthritis Res Ther. 2015 Dec 23;17:372. doi: 10.1186/s13075-015-0872-2.

    PMID: 26704522DERIVED

  • Tashkin DP, Volkmann ER, Tseng CH, Kim HJ, Goldin J, Clements P, Furst D, Khanna D, Kleerup E, Roth MD, Elashoff R. Relationship between quantitative radiographic assessments of interstitial lung disease and physiological and clinical features of systemic sclerosis. Ann Rheum Dis. 2016 Feb;75(2):374-81. doi: 10.1136/annrheumdis-2014-206076. Epub 2014 Dec 1.

    PMID: 25452309DERIVED

  • Theodore AC, Tseng CH, Li N, Elashoff RM, Tashkin DP. Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study. Chest. 2012 Sep;142(3):614-621. doi: 10.1378/chest.11-0801.

    PMID: 22156609DERIVED

  • Roth MD, Tseng CH, Clements PJ, Furst DE, Tashkin DP, Goldin JG, Khanna D, Kleerup EC, Li N, Elashoff D, Elashoff RM; Scleroderma Lung Study Research Group. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum. 2011 Sep;63(9):2797-808. doi: 10.1002/art.30438.

    PMID: 21547897DERIVED

  • Goldin J, Elashoff R, Kim HJ, Yan X, Lynch D, Strollo D, Roth MD, Clements P, Furst DE, Khanna D, Vasunilashorn S, Li G, Tashkin DP. Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study. Chest. 2009 Nov;136(5):1333-1340. doi: 10.1378/chest.09-0108.

    PMID: 19892673DERIVED

  • Goldin JG, Lynch DA, Strollo DC, Suh RD, Schraufnagel DE, Clements PJ, Elashoff RM, Furst DE, Vasunilashorn S, McNitt-Gray MF, Brown MS, Roth MD, Tashkin DP; Scleroderma Lung Study Research Group. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest. 2008 Aug;134(2):358-367. doi: 10.1378/chest.07-2444. Epub 2008 Jul 18.

    PMID: 18641099DERIVED

  • Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J, Clements P, Chung J, Elashoff RM, Suh R, Smith EA, Furst DE, Tashkin DP; Scleroderma Lung Study Research Group. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med. 2008 Jan 1;177(1):91-8. doi: 10.1164/rccm.200705-655OC. Epub 2007 Sep 27.

    PMID: 17901414DERIVED

  • Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, Goldin J, Arriola E, Strange C, Bolster MB, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel D, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Khanna D, Li N, Li G; Scleroderma Lung Study Research Group. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34. doi: 10.1164/rccm.200702-326OC. Epub 2007 Aug 23.

    PMID: 17717203DERIVED

MeSH Terms

Conditions

Lung DiseasesPulmonary FibrosisScleroderma, Systemic

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Respiratory Tract DiseasesLung Diseases, InterstitialFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsConnective Tissue DiseasesSkin and Connective Tissue DiseasesSkin Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Results Point of Contact

Title
Maureen Mayes, MD
Organization
University of Texas Health Science Center at Houston
Maureen.D.Mayes@uth.tmc.edu
+1 (713) 500-6900

Study Officials

  • Maureen Mayes

    The University of Texas Health Science Center, Houston

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Elizabeth Bidgood Chair in Rheumatology

Study Record Dates

First Submitted

February 9, 2000

First Posted

February 10, 2000

Study Start

August 1, 1999

Primary Completion

May 1, 2013

Study Completion

May 1, 2013

Last Updated

March 27, 2015

Results First Posted

March 6, 2015

Record last verified: 2015-03