Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00278525
Other study ID # DI Scl.Randomized2004
Secondary ID
Status Completed
Phase Phase 2
First received January 15, 2006
Last updated March 28, 2014
Start date September 2005
Est. completion date December 2012

Study information

Verified date March 2014
Source Northwestern University
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


Description:

To evaluate the efficacy of two treatment modalities: pulse cyclophosphamide versus high dose cyclophosphamide and anti-thymocyte globulin (ATG) rescued with autologous peripheral blood stem cell transplantation (PBSCT). The primary endpoints to be considered in this study are:

I)Time to Treatment Failure -Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:

1. Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart

2. Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart

3. Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months

4. Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition (TPN) for more than 12 months

II) Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests (DLCO, DLCO/VA, or FVC), or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath) that persists > 6 months or ability to wean off TPN


Recruitment information / eligibility

Status Completed
Enrollment 19
Est. completion date December 2012
Est. primary completion date September 2011
Accepts healthy volunteers No
Gender Both
Age group N/A to 60 Years
Eligibility Inclusion Criteria:

- Age 60 year or < 60 year old at the time of pretransplant evaluation.

- An established diagnosis of scleroderma.

- Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a Rodnan score of > 14

AND

Scleroderma with any one of the following:

- Diffusing capacity of the lung for carbon monoxide (DLCO) < 80% of predicted or decrease in lung function [DLCO, diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) ] of 10% or more over 12 months.

- Active alveolitis on bronchoalveolar lavage.

- Pulmonary fibrosis or alveolitis on computed tomography (CT) scan or chest x-ray (CXR) (ground glass appearance of alveolitis).

- Renal disease that is not explained by a bacterial infection or other renal disorders. (Subjects must have two or more of the following: proteinuria - greater than trace on dipstick, hematuria - urine blood on dipstick or sediment, hypertension that requires treatment with anti-hypertensive medications or untreated but with a diastolic blood pressure (BP) > 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 < 80% predicted or decrease in lung function (DLCO/VA,DLCO, FVC) of 10% or more in last 12 months.

Exclusion Criteria:

- Poor performance status Eastern Cooperative Oncology Group (ECOG 2) at the time of entry.

- Significant end organ damage such as:

1. Left Ventricular Ejection Fraction (LVEF) < 40% or deterioration of LVEF during exercise test on Multiple Gated Acquisition (MUGA) or echocardiogram.

2. Untreated life-threatening arrhythmia.

3. Active ischemic heart disease or heart failure.

4. End-stage lung disease characterized by total lung capacity (TLC) <45% of predicted value.

5. Pulmonary hypertension (systolic pulmonary arterial pressure > 40 mmHg or mean pulmonary arterial pressure (PAP) > 25 mmHG measurement by pulmonary arterial catheter).

6. Serum creatinine > 2.0 mg/dl.

7. Liver cirrhosis, transaminases > 3x of normal limits or bilirubin > 2.0 unless due to Gilberts disease.

8. Pericardial effusion> 200ml unless successful pericardiocentesis

9. Tricuspid annular peak systolic excursion (TAPSE) = 1.9 cm

10. 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 < 100,000/ul or absolute neutrophil count (ANC) < 1000/ul.

- Patients with duration of disease > 5 years.

- Exclude if > than 6 prior monthly IV cyclophosphamide treatments.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
standard of care
standard of care medication will be given
Procedure:
stem cell transplantation
The following is intervention: stem cell transplantation after conditioning regimen

Locations

Country Name City State
United States Northwestern University, Feinberg School of Medicine Chicago Illinois

Sponsors (1)

Lead Sponsor Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to Treatment Failure -Data are reporting number of participants that were classified as treatment failures
Time to Treatment Failure Definition-Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:
Failure of skin score (if > 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart
Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart
Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months
Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition(TPN) for more than 12 months
12 months No
Primary Disease Improvement Data are reporting number of participants that were classified as disease improvement.
Definition of disease improvement:
Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests [diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA), or forced vital capacity (FVC)], or in cardiac tests [pulmonary artery (PA) systolic pressure by right heart cath] that persists > 6 months or ability to wean off total parenteral nutrition (TPN)
12 months No
See also
  Status Clinical Trial Phase
Not yet recruiting NCT03629002 - BIOLOGICAL EXPLORATION OF THE VASCULAR FRACTION FROM THE ADIPOSE TISSUE OF PATIENTS WITH SCLERODERMIA
Terminated NCT00377455 - Placebo Controlled Trial of Bosentan in Scleroderma Patients Phase 2
Completed NCT00318188 - Effects of a Personalized Standardized Rehabilitation Program in Systemic Sclerosis N/A
Completed NCT03575156 - Microparticles's Role in the Pathophysiology of Systemic Lupus Erythematosus and Systemic Sclerosis N/A
Active, not recruiting NCT01413100 - Scleroderma Treatment With Autologous Transplant (STAT) Study Phase 2
Completed NCT00622895 - Allogeneic Hematopoietic Cell Transplantation for Severe Systemic Sclerosis Phase 1/Phase 2
Active, not recruiting NCT03816189 - Role of Eosinophil in Fibrogenesis of Systemic Sclerosis
Completed NCT01295736 - Sildenafil Effect on Digital Ulcer Healing in sClerodErma SEDUCE STUDY Phase 3
Completed NCT02213705 - Treatment of Refractory Sever Systemic Scleroderma by Injection of Allogeneic Mesenchymal Stem Cells Phase 1/Phase 2
Recruiting NCT03508375 - Evaluation of the Serum Soluble Fractalkine as a Biomarker of Pulmonary Fibrosis in Systemic Sclerosis N/A
Active, not recruiting NCT01309997 - Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease Phase 2
Completed NCT00697736 - Cardiac Repercussion of Systemic Sclerodermias N/A
Completed NCT02349009 - Trial of Topical C-82 in Systemic Sclerosis - A Phase I/II Biomarker and Safety Trial Phase 1/Phase 2
Completed NCT00318175 - Effect of Bosentan on Skin Fibrosis in Patients With Systemic Sclerosis Phase 2
Completed NCT03262922 - Clinical and Paraclinical Characteristics of the Systemic Scleroderma Cohort According to the Criteria ACR 2013 and the History of Professional Exposure or of Agricultural Environment
Recruiting NCT03816345 - Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer Phase 1
Recruiting NCT04380831 - TBI Using IMRT and Cyclophosphamide Prior to Stem Cell Transplant for the Treatment of Severe Systemic Sclerosis Early Phase 1
Terminated NCT00628797 - Effectiveness of UVA1-irradiation in the Treatment of Early Skin Fibrosis in Patients Suffering From Systemic Sclerosis Phase 1/Phase 2
Recruiting NCT05672992 - Longitudinal Spatial Frequency Domain Imaging Study N/A
Recruiting NCT05726630 - Clinical Study of Divozilimab in Patients With Systemic Scleroderma Phase 3