Phase 2
N=19
Cyclophosphamide and rATG With Hematopoietic Stem Cell Support in Systemic Scleroderma
SYSTEMIC SCLERODERMA
Bottom Line
View on ClinicalTrials.gov: NCT00278525 ↗Enrolled (actual)
19
Serious AEs
0.0%
Results posted
Apr 2014
Primary outcome: Primary: Time to Treatment Failure — 0; 8 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- standard of care (Drug); stem cell transplantation (Procedure)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Northwestern University
- Primary completion
- Sep 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Treatment Failure |
0; 8 | — |
| PRIMARY Disease Improvement |
10; 0 | — |
Summary
Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Once extensive cutaneous or visceral disease occurs, prognosis is significantly shorter than the general population. Although various treatments have been tried, none of them seems to have changed the natural history of scleroderma. Standard dose immunosuppressive treatment has been disappointing. Recently, cyclophosphamide at 1-2 mg/kg/day orally or 800-1400 mg intravenous (IV) monthly for 6-9 months has proven effective in treatment of scleroderma alveolitis (1). Recent phase I studies of immunoablation with autologous peripheral blood stem cell transplantation (PBSCT) showed some promising data, but the exact efficacy is undetermined (2,3). We now propose, as a phase II randomized study, autologous unmanipulated PBSCT versus pulse cyclophosphamide in patients with systemic scleroderma.
Eligibility Criteria
Inclusion Criteria
- Age 60 year or 14
AND
Scleroderma with any one of the following:
- Diffusing capacity of the lung for carbon monoxide (DLCO) 95 mm/hg.)
- Abnormal electrocardiogram (EKG) (non-specific ST-T wave abnormalities, low QRS voltage, or ventricular hypertrophy), or pericardial effusion or pericardial enhancement on magnetic resonance imaging (MRI)
- Gastrointestinal tract involvement confirmed on radiological study. Radiologic findings of scleroderma are small bowel radiographs showing thickened folds with dilated loops, segmentation, and flocculation +/- diverticulae, or pseudodiverticulae. A hide-bound appearance due to valvulae packing i.e. dilated and crowded circular folds, may be present. Gastrointestinal (GI) involvement may also be confirmed by D-xylose malabsorption, patulous esophagus, or esophageal manometry.
OR
As published in NEJM, 2006, 345:25 2655-2709. Limited or diffuse SSL with lung involvement defined as active alveolitis on bronchoalveolar lavage (BAL) or ground-glass opacity on CT, a DLCO 40 mmHg or mean pulmonary arterial pressure (PAP) > 25 mmHG measurement by pulmonary arterial catheter).
- Serum creatinine > 2.0 mg/dl.
- Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless due to Gilberts disease.
- Pericardial effusion> 200ml unless successful pericardiocentesis
- Tricuspid annular peak systolic excursion (TAPSE) ≤ 1.9 cm
- MRI of heart showing D sign (intraventricular flattering)
- Human immunodeficiency virus (HIV) positive.
- Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment.
- Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
- Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- Inability to give informed consent.
- Major hematological abnormalities such as platelet count 5 years.
- Exclude if > than 6 prior monthly IV cyclophosphamide treatments.
Data sourced from ClinicalTrials.gov (NCT00278525). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.