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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Karolinska Institutet
Sponsor:
Information provided by (Responsible Party):
Jonas Mattsson, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT00993343
First received: October 9, 2009
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Graft-versus-host Disease
Survival
Drug: Sirolimus/tacrolimus
Drug: cyclosporine/methotrexate
Phase 3

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • The primary endpoint is grade II-IV acute GVHD [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
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)
Arms Assigned Interventions
Active Comparator: Cyclosporine + Methotreaxte Drug: cyclosporine/methotrexate
Standard GVHD prophylaxis
Active Comparator: sirolimus + tacrolimus Drug: Sirolimus/tacrolimus
Standard GVHD prophylaxis

Detailed Description:

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

  1. Time to neutrophils >0.5 x 109/L.
  2. Time to platelets >20 x 109/L and 50 x 109/L.
  3. Platelet level 30 days after transplant.
  4. Transfusion requirements of platelets, erythrocytes, granulocyte transfusions during the first 30 days.
  5. Non-engraftment (graft failure/rejection).
  6. Grade of acute GVHD.
  7. Incidence of chronic graft-versus-host disease graded as limited or extensive and mild, moderate and severe.
  8. Transplant-related mortality.
  9. Probability of relapse in patients with haematological malignancies.
  10. Survival.
  11. Relapse-free survival.
  12. Infections by bacteria, virus and fungi. Cytomegalovirus reactivation is also followed by PCR.
  13. 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

  Eligibility

Ages Eligible for Study:   6 Months to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993343

Contacts
Contact: Olle Ringden, M.D. Ph.D. +46-8-58582672 Olle.Ringden@ki.se

Locations
Sweden
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.         
Sponsors and Collaborators
Karolinska Institutet
Investigators
Principal Investigator: Olle Ringden, M.D. Ph.D. Karolinska Institutet
  More Information

No publications provided

Responsible Party: Jonas Mattsson, Medical Director, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT00993343     History of Changes
Other Study ID Numbers: 070101
Study First Received: October 9, 2009
Last Updated: December 8, 2013
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by Karolinska Institutet:
GVHD
tacrolimus
sirolimus
cyclosporine
allogeneic
stem cell transplantation
Relapse-free survival

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Cyclosporine
Cyclosporins
Everolimus
Methotrexate
Sirolimus
Tacrolimus
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014