Back to results

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

Primary Purpose

Graft-versus-host Disease, Survival

Status

Completed

Phase

Phase 3

Locations

Sweden

Study Type

Interventional

Intervention

Sirolimus/tacrolimus

cyclosporine/methotrexate

About this trial

This is an interventional prevention trial for Graft-versus-host Disease focused on measuring GVHD, tacrolimus, sirolimus, cyclosporine, allogeneic, stem cell transplantation, Relapse-free survival

Eligibility Criteria

6 Months - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Karolinska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Cyclosporine + Methotreaxte

sirolimus + tacrolimus

Arm Description

Outcomes

Primary Outcome Measures

The primary endpoint is grade II-IV acute GVHD

Secondary Outcome Measures

Relapse-free survival

Survival

Full Information

NCT ID

NCT00993343

First Posted

October 9, 2009

Last Updated

April 13, 2015

Sponsor

Karolinska Institutet

1. Study Identification

Unique Protocol Identification Number

NCT00993343

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

September 2007 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Karolinska Institutet

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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 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. Survival. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft-versus-host Disease, Survival

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

215 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cyclosporine + Methotreaxte

Arm Type

Active Comparator

Arm Title

sirolimus + tacrolimus

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Sirolimus/tacrolimus

Intervention Description

Standard GVHD prophylaxis

Intervention Type

Drug

Intervention Name(s)

cyclosporine/methotrexate

Intervention Description

Standard GVHD prophylaxis

Primary Outcome Measure Information:

Title

The primary endpoint is grade II-IV acute GVHD

Time Frame

One year

Secondary Outcome Measure Information:

Title

Relapse-free survival

Time Frame

2 years

Title

Survival

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olle Ringden, M.D. Ph.D.

Organizational Affiliation

Karolinska Institutet

Official's Role

Principal Investigator

Facility Information:

Facility Name

Karolinska University Hospital

City

Stockholm

ZIP/Postal Code

14186

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

30710687

Citation

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.

Results Reference

derived

PubMed Identifier

27662016

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs