Scleroderma: Cyclophosphamide or Transplantation
Condition: Scleroderma, Systemic; Sclerosis; Autoimmune Disease
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Autoimmune Diseases; Sclerosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      SCOT is a clinical research study designed for people with severe forms of scleroderma. SCOT
      stands for Scleroderma: Cyclophosphamide Or Transplantation. The SCOT study will compare the
      potential benefits of stem cell transplant and high-dose monthly cyclophosphamide (Cytoxan)
      in the treatment of scleroderma.
    

Detailed description: 
      Severe systemic sclerosis (SSc) is a serious autoimmune disorder in which a person's own
      immune cells attack organs in the body. SSc affects the skin, joints, lungs, heart,
      intestinal tract, and kidneys, and half of the patients with the most severe organ
      involvement die within 5 years. Treatment for SSc usually includes supportive care or
      immunosuppressive drugs (drugs to suppress the immune system). As the immune cells are
      believed to be causing the disease, researchers are looking for new therapies that either
      slow down or stop this process, while not being too toxic.

      The main purpose of this study is to determine the safety and effectiveness of high-dose
      immunosuppressive therapy followed by reinfusion (transplantation) of the participant's own
      autologous (self) peripheral blood stem cells (PBSCs) compared to treatment with monthly (for
      12 months) intravenous doses of cyclophosphamide (Cytoxan) therapy for the treatment of
      severe systemic sclerosis (SSc). These treatments are being given in order to determine if
      they will slow down or stop SSc from becoming more severe, and if they can reverse the
      effects of the disease. The researchers are evaluating the effects of the two treatments on
      serious organ damage and survival related to SSc, while also looking at the side effects of
      the two treatments.

      This trial also includes three optional mechanistic sub-studies open to a subset of
      participants enrolled in the SCOT trial:

        1. Pharmacokinetics of 4-hydroxycyclophosphamide in Patients Receiving Cyclophosphamide for
           the SCOT trial (Originally listed separately as DAIT SCSSc-01-01, NCT00848614). The
           purpose of this study is to determine the plasma concentration and exposure time
           required for cyclophosphamide to produce optimal immunosuppressive activity with minimal
           toxicity in participants with severe systemic sclerosis.

        2. Vascular Progenitor Cells and the Pathogenesis of Systemic Sclerosis(Originally listed
           separately as DAIT SCSSc-01-02, NCT00871221). The purpose of this study is to measure
           and characterize the circulating endothelial progenitor cells from the blood of 30
           participants and also to determine the extent of vascular cell apoptosis and
           proliferation in cutaneous microvasculature in these participants before and after the
           receipt of the two SCOT treatment regimens.

        3. Molecular Analysis of T Cell Immune Recovery for the SCOT Trial(Originally listed
           separately as DAIT SCSSc-01-03, NCT00872508). The purpose of this study is [1] to
           describe the condition of peripheral T cell reactivity and repertoire diversity in SSc
           patients and evaluate evidence for potential defects prior to randomization, [2] to gain
           a better understanding of the impact of cyclophosphamide (Cytoxan) and high-dose
           immunosuppressive therapy with autologous stem cell transplantation on thymopoiesis, and
           [3] to describe the kinetics and breadth of T cell immune recovery in SSc patients
           treated with these interventions.
    

Intervention name(s): mHSCT; cyclophosphamide
Intervention type(s): Biological; Drug
Intervention description(s): Hematopoietic progenitors were mobilized with G-CSF. After leukapheresis and CD34+ cell enrichment, the autologous product was cryopreserved. Fractionated TBI (800 cGy), CY (120 mg/kg) and equine antithymocyte globulin (90 mg/kg) were administered as previously reported (References provided in citation section of this ClinicalTrials.gov record: PubMed ID: 17452515 citation and 2.) PubMed ID: 12176878 citation).; An initial intravenous dose of 500 mg/m^2 was followed by 11 infusions of 750 mg/m^2 with mesna given for bladder protection.
Other intervention name(s): Myeloablative Hematopoietic Stem Cell Transplant; cytoxan; CY
Intervention MeSH terms: Cyclophosphamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: systemic sclerosis; hematopoietic stem cell transplant; clinical trial; global rank composite score