Randomized Trial Comparing Sirolimus and Tacrolimus Versus Cyclosporine and Methotrexate as Graft-versus-host Disease (GVHD) Prophylaxis After Allogeneic Stem Cell Transplantation
To evaluate if rapamune + tacrolimus immunosuppressive prophylaxis is better than the established therapy using cyclosporine and methotrexate, a Nordic prospective multicenter randomized study will be performed. Patients will be randomized to treatment with rapamune combined with tacrolimus, or the established therapy using cyclosporine and methotrexate.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Prospective Randomized Study Comparing Rapamune and Tacrolimus vs. Cyclosporine and Methotrexate as Immune Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation, Using HLA-A, -B, -DRβ1 Identical Related or Unrelated Donors. A Nordic Multicenter Study.|
- The primary endpoint is grade II-IV acute GVHD [ Time Frame: One year ] [ Designated as safety issue: No ]
- Relapse-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||September 2007|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Cyclosporine + Methotreaxte||
Standard GVHD prophylaxis
|Active Comparator: sirolimus + tacrolimus||
Standard GVHD prophylaxis
Primary endpoint The primary endpoint is grade II-IV acute GVHD in the two groups. GVHD is diagnosed clinically and graded from 0 to IV. The diagnosis is clinical and biopsies from skin, liver and gut is used according to the routines at each participating center.
Other study parameters
- Time to neutrophils >0.5 x 109/L.
- Time to platelets >20 x 109/L and 50 x 109/L.
- Platelet level 30 days after transplant.
- Transfusion requirements of platelets, erythrocytes, granulocyte transfusions during the first 30 days.
- Non-engraftment (graft failure/rejection).
- Grade of acute GVHD.
- Incidence of chronic graft-versus-host disease graded as limited or extensive and mild, moderate and severe.
- Transplant-related mortality.
- Probability of relapse in patients with haematological malignancies.
- Relapse-free survival.
- Infections by bacteria, virus and fungi. Cytomegalovirus reactivation is also followed by PCR.
- Side-effects. Side-effects regarding hematopoiesis, liver test, renal function, cardiac function, neurology, endocrinology, etc., are taken from the patients' charts. These parameters are followed regularly after transplantation.
Inclusion criteria Chronic myeloid leukemia (CML) in 1st or 2nd chronic phase, acute myeloid leukemia (AML) in complete remission, acute lymphoblastic leukemia (ALL) in complete remission, myelodysplastic syndrome, chronic lymphocytic leukemia, lymphoma, non-malignant disorders, severe aplastic anemia, hemoglobinopathies and metabolic disorders
|Contact: Olle Ringden, M.D. Ph.D.||+46-8-58582672||Olle.Ringden@ki.se|
|Karolinska University Hospital||Recruiting|
|Stockholm, Sweden, 14186|
|Contact: Olle Ringden, M.D. Ph.D. +46-8-58582672 Olle.Ringden@ki.se|
|Sub-Investigator: Jonas Mattsson, M.D. Ph.D.|
|Principal Investigator: Olle Ringden, M.D. Ph.D.|
|Principal Investigator:||Olle Ringden, M.D. Ph.D.||Karolinska Institutet|