Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NST) for Patients With Systemic Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Scleroderma
- Sponsor
- Richard Burt, MD
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Survival; Disease improvement;Time to disease progression
- Status
- Terminated
- Last Updated
- 13 years ago
Overview
Brief Summary
Scleroderma is disease believed to be due to immune cells, cells which normally protect the body but are now causing damage to the body. There has not been any treatment that has been effective in treating this disease. The likelihood of progression of the disease to severe disability and death is high. This study is designed to examine whether treating patients with high dose Cyclophosphamide and Fludarabine (drugs which reduce the function of your immune system) and CAMPATH-1H (a protein that kills the immune cells that are thought to be causing the disease), followed by return of blood stem cells that have been previously collected from patients brother or sister will stop or reverse the disease. The purpose of the Cyclophosphamide, Fludarabine and CAMPATH-1H is to decrease immune system. The purpose of the stem cell infusion is to restore blood production, which will be severely impaired by the Cyclophosphamide, Fludarabine and CAMPATH-1H, and to produce a normal immune system that will no longer attack the body.
Investigators
Richard Burt, MD
MD
Northwestern University
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 55 years old
- •An established diagnosis of scleroderma (84)
- •Diffuse cutaneous scleroderma with involvement proximal to the elbow or knee and a Rodnan score (see Appendix III) of \> 14 (85)
- •And one of the following:
- •DLCO \< 80% of predicted or decrease in lung function (TLC, DLCO or FEV1) of 10% or more over 12 months
- •Active alveolitis on bronchoalveolar lavage
- •Pulmonary fibrosis or alveolitis on CT scan or CXR
- •Elevated ESR greater than or equal to 25mm/hour confirmed on a second occasion at least two weeks apart without evidence of active infectious process.
- •Abnormal EKG (low QRS voltage, or ventricular hypertrophy) or left ventricle (LV) diastolic dysfunction (expressed by an inverted E/A ratio which represents early and late filling of the LV during atrial contraction) or LV wall thickness
- •Since pulmonary disease independent of skin score (NEJM, 2006, 345:25 2655-2709) carries a poor prognosis, patient may be enroled for only lung involvement defined as active alveolitis on BAL or ground-glass opacity on CT, a DLCO \< 80% predicted or decrease in lung function (TLC), DLCO, FVC) of 10% or more in last 12 months.
Exclusion Criteria
- •Poor performance status (ECOG \> or =2) at the time of entry, unless due to disease.
- •Significant end organ damage such as:
- •LVEF \<40% or deterioration of LVEF during exercise test on MUGA or echocardiogram
- •Untreated life-threatening arrhythmia
- •Active ischemic heart disease or heart failure
- •DLCO less than 45% of predicted value, unless due to disease.
- •Pulmonary hypertension (estimated systolic pulmonary arterial pressure \>40 mmHg by Doppler echocardiography or 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
- •HIV positive
Outcomes
Primary Outcomes
Survival; Disease improvement;Time to disease progression
Time Frame: 5 years after transplant