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

NCT00993343 | Completed Phase 3 DMC

• 1 other identifier: 070101
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Graft-versus-host Disease; Survival

Keywords

GVHD; tacrolimus; sirolimus; cyclosporine; allogeneic; stem cell transplantation; Relapse-free survival

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is grade II-IV acute GVHD

  One year

Secondary Outcomes (2)

• Relapse-free survival

  2 years

• Survival

  2 years

Study Arms (2)

Cyclosporine + Methotreaxte

ACTIVE COMPARATOR

Drug: cyclosporine/methotrexate

sirolimus + tacrolimus

ACTIVE COMPARATOR

Drug: Sirolimus/tacrolimus

Interventions

Sirolimus/tacrolimus DRUG

Standard GVHD prophylaxis

sirolimus + tacrolimus

cyclosporine/methotrexate DRUG

Standard GVHD prophylaxis

Cyclosporine + Methotreaxte

Eligibility Criteria

• Age: 6 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, Stockholm County, 14186, Sweden

Location

Related Publications (2)

• Torlen J, Gaballa A, Remberger M, Mork LM, Sundberg B, Mattsson J, Uhlin M. Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019 Jun;25(6):1260-1268. doi: 10.1016/j.bbmt.2019.01.029. Epub 2019 Jan 30.

  PMID: 30710687 DERIVED

• Torlen J, Ringden O, Garming-Legert K, Ljungman P, Winiarski J, Remes K, Itala-Remes M, Remberger M, Mattsson J. A prospective randomized trial comparing cyclosporine/methotrexate and tacrolimus/sirolimus as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation. Haematologica. 2016 Nov;101(11):1417-1425. doi: 10.3324/haematol.2016.149294. Epub 2016 Aug 4.

  PMID: 27662016 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sirolimus; Tacrolimus; Cyclosporine; Methotrexate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Olle Ringden, M.D. Ph.D.

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: September 1, 2007
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 14, 2015

Record last verified: 2015-04

Locations

SE (1)