The present project is a multicenter phase II trail aiming at comparing which of the two postgrafting immunosuppressive regimens proposed in this study will be best suited to prevent graft-versus-host disease (GVDH). The immunosuppressive regimens will consist of: Tacrolimus plus Mycophenolate Mofetil or Tacrolimus plus Sirolimus. Before grafting patients will undergo a reduced-intensity conditioning with Fludarabine/total body irradiation (TBI) or Fludarabine/Busulfan/anti-thymoglobuline. Following the interim analysis of October 2014, the protocol has been amended to allow inclusion only after Flu-TBI conditioning. The hypothesis is that the Tacrolimus plus Sirolimus regimen will be associated with better progression-free survival due to a lower incidence of relapse/progression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
200
Tablets. For HLA-identical sibling donors:15 mg/kg t.i.d from day 0 to day 28. For alternative donor: 15 mg/kg, from day 0 to day 42.
Tablets. 6 mg loading dose on day -3, followed by (1)-2 mg daily to a target trough level of 5 to 10 ng/mL. Full doses will be given until day 100 (sibling recipients) or 180 (alternative donor recipients). Doses will then be progressively tapered to be definitely discontinued by day 180 (sibling donors) or 365 (alternative donor recipients) in the absence of GVHD.
Ziekenhuis Netwerk Antwerpen (ZNA)
Antwerp, Antwerpen, Belgium
University Hospital, Antwerp
Edegem, Antwerp, Belgium
Jules Bordet Institute
Brussels, Brabant, Belgium
AZ VUB Jette
Brussels, Brussels Region Capital, Belgium
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Brussels, Brussels Region Capital, Belgium
Queen Fabiola Children's University Hospital
Brussels, Brussels, Region Capital, Belgium
University Hospital, Gasthuisberg
Leuven, Flamish Brabant, Belgium
UZ Gent
Ghent, Flanders Ost, Belgium
Jolimont Hospital Haine Saint Paul
Haine St-Paul, Hainaut, Belgium
Cliniques Universitaires de Mont-Godinne
Yvoir, Namur, Belgium
...and 3 more locations
Progression-free survival
To compare the 1-year progression-free survival between the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 1 year after transplantation
Relapse rate; nonrelapse mortality and overall survival
To compare relapse rate, nonrelapse mortality, and overall survival in the 2 prophyltic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) 1, 2 and 5 years after hematopietic stem cell transplantation (HSCT) in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 1, 2 and 5 years after transplantation
Progression free survival
To compare progression-free survival in the 2 phrophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus) 2 and 5 years after HSCT, in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 2 and 5 years after transplantation
Engraftment
To compare hematopoietic (whole blood and T cell chimerism) engraftment and to evaluate the 1-year incidence of graft rejection in the 2 prophylctic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 1 year after transplantation
Acute GVDH
To compare the 6-mo incidence of grades II-IV and III-IV acute GVHD in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 6 months after transplantation
Chronic GVDH
To compare the 1-yr incidence of chronic GVHD in the phrophylactic 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 1 year after transplantation
Immunological reconstitution
To compare the quality and timing of immunologic reconstitution in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus),in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 3 mo, 6 mo, 1 yr, 2 yrs and 5 yrs after transplantation
Infection
To compare the 1-yr incidences of bacterial, fungal and viral infections in the 2 prophylactic arms (Tracolimus/Mycophenolate Mofetil and Tracolimus/Sirolimus), in the whole group of patients and separately in those conditioned with Fluradabine/TBI or Fluradabine plus Busulfan and anti-thymocyte globulin.
Time frame: 1 year after transplantation
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