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ASTIS Study
High Dose Immunoablation and Hematopoietic Stem cell Transplantation versus Monthly Intravenous Pulse Therapy Cyclophosphomide in Severe Systemic Sclerosis.
This study is sponsored by the European Group for Blood & Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) Scleroderma Study Group.
This study is currently recruiting patients.
Study Design
Purpose
Additional Study Details
Eligibility
Location and Contact Info
Related Articles
Study Design
This is a multicenter, prospective, controlled, randomized, phase III study comparing high dose immunoablation and autologous hematopoietic stem cell transplantation with monthly pulse therapy Cyclophosphomide in patients with severe systemic sclerosis.
ASTIS Trial. A multicenter, prospective randomized phase III study to compare efficacy and safety of high dose immunoablation and autologous hematopoietic stem cell transplantation with intravenous pulse therapy cyclophosphamide for the treatment of patients with severe systemic sclerosis. ASTISTrial. 07/11/08.
Purpose
The purpose of this research study is to compare the effectiveness and safety of two different treatments in patients with severe systemic sclerosis. Both treatments contain the chemotherapy drug cyclophosphamide. One of the treatments is cyclophosphamide given monthly for 12 months (pulse therapy). Pulse therapy with cyclophosphamide, although not curative, is thought to be the best known treatment for systemic sclerosis. Because some patients do not respond to pulse therapy or only have a short response, new treatments are being studied.
The other treatment in this study is one of those being studied. This treatment is “called high dose immunoablation and autologous stem cell transplantation”. Immunoablation means “to get rid of immune cells” thought to be causing sclerosis. This is done with a high dose of cyclophosphamide and another medication, anti-thymocyte globulin (ATG). ATG is a rabbit protein that helps to lower the number of immune cells. This will be followed by an infusion of special blood cells that were previously donated by the patient. These cells are called autologous stem cells. The stem cells will grow into new immune cells that will slow the progression of the sclerosis.
Additional Study Details
Cardiopulmonary function before and after cyclophosphamide treatment in severe systemic sclerosis: comparison of monthly intravenous bolus and autologous haematopoietic stem cell transplantation. In spite of higher cyclophosphamide doses during autologous haematopoietic stem cells transplantation than bolus treatment, cardiopulmonary toxicity appeared not to be increased. The ongoing European ASTIS trial will compare the respective benefits of these 2 cyclophosphamide regimens in severe systemic sclerosis. PubMed. Rev Med Interne. 2005 Jun;26(6):444-452. (Also see: Stem Cell Transfusions)
Patients with severe systemic sclerosis will under go a prestudy evaluation, which includes a detailed physical exam, laboratory testing, skin biopsies, x-rays, CT Scans, Electrocardiograms, Dental Consult and a bone marrow aspiration to determine if they meet eligibility requirements. Patients will sign an informed consent prior to any screening procedures. All patients who meet the eligibility criteria will be registered and randomized to one of the following treatment groups.
A. High dose immunoablation and autologous stem cell transplantation (investigational treatment)
Treatment A will consist of 4 steps: mobilization, leukapheresis, conditioning, and autologous stem cell infusion: Patients will need central venous catheter placement prior to starting treatment and will require hospitalization for conditioning and autologous stem cell infusion.
  • Mobilization refers to increasing the number of stem cells in blood. Mobilization of stem cells will be done by giving two intravenous doses of cyclophosphamide 2g/m2 (one each day for two days). The patient will also receive Mesna and hyperhydration for bladder protection. Five days following mobilization they will receive filgrastim (G-CSF) 10 mcg/kg/day for five days given as an injection under the skin. Filgrastim is a medicine given to further increase the number of stem cells in the blood. Blood counts will be monitored daily.
  • Leukapheresis is the procedure by which the stem cells are separated from the rest of the blood. This is done by removing blood through a catheter and putting it through a machine that removes the stem cells; the blood is then returned to the patient. This usually takes 2-3 hours a day for 2-5 days. The stem cells are then processed, frozen and stored until it is time for transplant.
  • Conditioning refers to the administration of cyclophosphamide and Antithymocyte Globulin (ATG). Cyclophosphamide 50 mg/kg/day will be given intravenously once daily for 4 days. ATG 2.5 mg/kg/day will be given intravenously, once a day for 3 days. They will also be given methylprednisone 1mg/kg to reduce the side effects caused by ATG.
  • Autologous stem cell infusion will occur at least 48 hours after the last dose of cyclophosphamide. The autologous stem cells previously collected and frozen will be thawed and infused similar to a blood transfusion. The patients will be in the hospital to receive the stem cell infusion. After the infusion of stem cells, they will continue to be hospitalized so they can be monitored and treated for complications. After discharge from the hospital, patients will be followed in the outpatient clinic frequently until they are stable to return to their local oncologist.
B. Pulse Therapy (standard treatment)
Patients will receive 12 monthly single infusions of cyclophosphamide 750 mg/m2. Patients will receive IV hydration and Mesna will be given to protect the bladder. This may be given in the outpatient clinic or during a short hospital stay.
Eligibility
Inclusion:

1. Age between 16 and 60 years
2. Diagnosis of systemic sclerosis according to ARA-criteria
3. Diffuse scleroderma with disease duration </= 4 years since development of the skin thickening plus a modified Rankin skin score >/= 15 plus major organ involvement as defined as:

a. DLCO and/or (F)VC </= 70% and evidence of interstitial lung disease
b. Renal involvement = any of the following: Hypertension, urinalysis abnormalities, new renal insufficiency
c. Cardiac involvement = any of the following: reversible congestive heart failure, atrial or ventricular rhythm disturbances such as recurrent episodes of atrial fibrillation or flutter
d. Informed Consent

Exclusion:

1. Pregnancy or unwillingness to use contraception during study

2. Concomitant severe disease:

a. respiratory
b. renal
c. cardiac
d. liver failure
e. psychiatric disorders
f. other neoplasms or myelodysplasia
g. uncontrolled hypertension
h. uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity

3. Previous treatment with TLI, TBI or alkylating agents including cyclophosphamide

4. Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride, trichlorethylene or silica: eosinophilic myalgia syndrome; eosinophilic fasciitis

Expected Total Enrollment: 6
Location and Contact Information
H. Lee Moffitt Cancer Center and Research Institute
12902 Magnolia Drive
Tampa, FL 33612 United States Research Coordinator: Dawn Garrett, L.P.N., CTC
Phone: 813-979-7227,
Email garretdl@moffitt.usf.edu

Principal Investigator: Karen K. Fields, M.D.
Co-Investigator: Frank Vasey, M.D.
Co-Investigator: Teresa Field, M.D., Ph.D.
Co- Investigator: Melissa Alsina, M.D.
Co-Investigator: Steven Golstein, M.D.
Co- Investigator: William Dalton, M.D.
Co- Investigator: Clayton Smith, M.D.
Co-Investigator: Daniel Sullivan, M.D.
Co-Investigator: Thomas Loughran, M.D.

Related Articles
Redcar woman taking part in world-first scleroderma treatment study. The pioneering Autologous Stem Cell Transplantation International Scleroderma Trial (ASTIS) involves 150 patients at 26 European centres and five UK centres. The trial’s aim is to compare the effect and benefits of the two treatments. The first results are expected by 2010. Gazette Live. Marie Levy. 07/24/09.
High Dose Cyclophosphamide (CYC) Without Stem Cell Transplantation in Systemic Sclerosis. High dose CYC without stem cell transplantation leads to rapid improvement of the modified Rodnan skin, HAQ, and PGA scores in the severe early diffuse SSc. Christopher V. Tehlirian. 689 ACR 2006. (Also see: Cytoxan, SCOT Clinical Trial, and Skin Fibrosis)
This page was posted on this site at the request of Dawn Garrett as a courtesy of the nonprofit International Scleroderma Network. At our option, we offer to make and post free web pages for any scleroderma group in the world. The ISN does not endorse any scleroderma treatment or clinical trial. See disclaimer. Page posted 2-19-03.
 
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