Phase II Pilot Study of Cyclophosphamide and Rabbit Anti-Thymocyte Globulin as Salvage Therapy in Patients With Diffuse Systemic Sclerosis

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2

Conditions: Systemic Sclerosis

Treatments: Drug: anti-thymocyte globulin; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT00016458

FHCRC-1473.00

199/15818

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: Under 64 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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