Randomized Trial Comparing Sirolimus and Tacrolimus Versus Cyclosporine and Methotrexate as Graft-versus-host Disease (GVHD) Prophylaxis After Allogeneic Stem Cell Transplantation

• Status: Completed
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Karolinska Institutet
• Treatments: Cyclosporine; Cyclosporins; Everolimus; Methotrexate; Sirolimus; Tacrolimus

Criteria

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

Exclusion Criteria:

• Recipients of major HLA-mismatched grafts.

• Patients who are addicted to drugs or alcohol.

• Patients who receive other stem cell source than bone marrow or peripheral stem cells, for instance cord blood transplants.

• Patients with relapse or blast crisis of their malignant disease.

• Prior allogeneic transplant using any hematopoietic stem cell source

• Seropositive for the human immunodeficiency virus (HIV)

• Uncontrolled bacterial, viral, or fungal infection (progression of clinical symptoms) Pregnant (positive serum human chorionic gonadotropin [β-HCG] test) or breastfeeding within 4 weeks of study entry

• Kidney function: serum creatinine outside the normal range for age, or measured creatinine clearance less than 40 mL/min/1.72m² within 4 weeks of study entry and proteinuria >0.3 g/day

• Liver function: most recent direct bilirubin, ALT, or AST greater than two times the upper limit of normal within 4 weeks of study entry

• Lung disease: in adults, FVC or FEV1 less than 60% of predicted value (corrected for hemoglobin); in children, overt hypoxemia, as measured by an oxygen saturation of less than 92% within 4 weeks of study entry

• Cardiac ejection fraction of less than 45% in adults and children, or less than 26% shortening fraction in children within 4 weeks of study entry

• Cholesterol level greater than 300 mg/dL or triglyceride level greater than 300 mg/dL while being treated, or not on appropriate lipid-lowering therapy within 4 weeks of study entry

• Karnofsky score <70%

• Prior history of allergy to sirolimus

• Requires voriconazole at time of study entry

• Currently receiving another investigational drug unless cleared by the principal investigator and sponsor

• Patients receiving BuCy as conditioning therapy