OBJECTIVES: I. Determine the toxicity of cyclophosphamide and rabbit anti-thymocyte globulin in patients with diffuse systemic sclerosis. II. Determine the efficacy of this regimen in terms of controlling disease in these patients.

Condition	Treatment or Intervention	Phase
Systemic Sclerosis	Drug: anti-thymocyte globulin  Drug: cyclophosphamide	Phase II

Further Study Details: 

Expected Total Enrollment:  20

PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1-2 hours on day 1 and rabbit anti-thymocyte globulin IV over 6-8 hours on days 2-5. Patients are followed on days 60-85 and then every 3 months for 1 year.

Ages Eligible for Study:  up to  64 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of diffuse systemic sclerosis

Progressive disease Skin score at least 16 Interstitial or pulmonary vasculitis (FVC or DLCO no greater than 70% predicted) with evidence of alveolitis by bronchoalveolar lavage (BAL) Proteinuria (more than 500 mg/24 hours) Rapid deterioration in pulmonary function (at least 15% decrease in FVC or DLCO within the past 6 months) or new evidence of alveolitis by CT scan changes or BAL

No acute renal failure secondary to systemic sclerosis crisis

DLCO greater than 20% predicted

Ineligible for or refused autologous or allogeneic peripheral blood stem cell or bone marrow transplantation

--Prior/Concurrent Therapy--

Endocrine therapy: Concurrent prednisone allowed if prior chronic use

Other: At least 4 days since prior immunosuppressive therapy

--Patient Characteristics--

Performance status: Karnofsky 50-100%

Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3

Hepatic: Bilirubin less than 2.5 times upper limit of normal (ULN) SGOT less than 2.5 times ULN

Renal: See Disease Characteristics Creatinine clearance at least 35 mL/min No requirement for renal dialysis

Cardiovascular: Ejection fraction greater than 45% No myocardial infarction within the past 12 months No unstable angina No uncontrolled cardiac arrhythmias No evidence of congestive heart failure

Pulmonary: See Disease Characteristics

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active uncontrolled infection
• No hypersensitivity to rabbit proteins
• No prior hemorrhagic cystitis requiring transfusion
• No concurrent active hemorrhagic cystitis by cystoscopy (if prior history)
• No concurrent malignancy

Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

Leona Holmberg,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  199/15818; FHCRC-1473.00
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  May 6, 2001
ClinicalTrials.gov Identifier:  NCT00016458
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08