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

April 13, 2015 updated by: Jonas Mattsson, Karolinska Institutet

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.

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

215

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 14186
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cyclosporine + Methotreaxte
Drug: cyclosporine/methotrexate
Standard GVHD prophylaxis
Active Comparator: sirolimus + tacrolimus
Drug: Sirolimus/tacrolimus
Standard GVHD prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint is grade II-IV acute GVHD
Time Frame: One year
One year

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: 2 years
2 years
Relapse-free survival
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Investigators

  • Principal Investigator: Olle Ringden, M.D. Ph.D., Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

October 9, 2009

First Submitted That Met QC Criteria

October 9, 2009

First Posted (Estimate)

October 12, 2009

Study Record Updates

Last Update Posted (Estimate)

April 14, 2015

Last Update Submitted That Met QC Criteria

April 13, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 070101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe