Clinical trial NCT01445821
Conditions: Scleroderma, Systemic
Keywords: Autologous Stem Cell Transplantation
Sponsor: Northwestern University
Start date: 2011-09-15; Completion date: 2019-10-10
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
ASSIST I was the first randomized trial in patients with scleroderma to not just slow disease progression but rather actually reverse it. It is the first treatment to have ever demonstrated reversal of lung disease in scleroderma with improvement in FVC, total lung capacity (TLC), high-resolution computed tomography (HRCT), and QOL. We now, therefore, purpose to compare the ASSIST I conditioning regimen of cyclophosphamide and rATG to a less intense regimen of rATG/cyclophosphamide/Fludarabine. In the new regimen the cyclophosphamide dose is decreased to 120mg/kg (60mg/kg/day x 2) compared to 200mg/kg (50mg/kg/day) in the standard regimen. The lower dose of cyclophosphamide will be less cardiotoxic. This study will determine if the less cardiotoxic regimen will be safer than the standard regimen and as effective as the standard regimen.

Detailed description:
Mobilization. For patients in both arms undergoing hematopoietic stem cell transplantation (HSCT), peripheral blood stem cells (PBSC) will be mobilized with cyclophosphamide (2 g/m2) followed by 5-10 mcg/kg subcutaneous filgrastrim daily from day 5 until completion of apheresis. Mobilized hematopoietic stem cells (HSC) will be collected by apheresis on day 10 and cryopreserved without selection or manipulation. There will be an interval of at least 17 days between mobilization of PBSC and start of conditioning regimen.

Arms: arm 1: The control arm will have the same conditioning regimen used in ASSIST study. The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment. arm 2: The conditioning regimen will be 120 mg/kg of intravenous cyclophosphamide given in 2 equal fractions on days -3 and -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. PBSC will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Interventions: intervention 1: Peripheral Blood Stem Cells intervention 2: Cyclophosphamide intervention 3: Mesna intervention 4: rATG intervention 5: Methylprednisolone intervention 6: Filgrastim intervention 7: Fludarabine
Intervention descriptions: intervention 1: Mobilized leukapheresis product intervention 2: An alkylating agent which causes prevention of cell division by forming adducts with DNA intervention 3: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis intervention 4: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells intervention 5: Steroid intervention 6: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream intervention 7: Purine analog which inhibits DNA synthesis or repair

Protocol documents: