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Graft-versus-host DiseasePhase 3NCT00993343

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

A Phase 3 study testing Sirolimus/tacrolimus and cyclosporine/methotrexate in people with Graft-versus-host Disease and Survival, run by Karolinska Institutet at 1 site in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 75 years
Conditions the study is for
Graft-versus-host Disease, Survival
What is being tested?
Sirolimus/tacrolimus and cyclosporine/methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
215 participants
Where
1 siteSweden
Study dates
Sep 2007to Apr 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Sweden1 site

  • Karolinska University Hospital

    Stockholm, Stockholm County, 14186

Other trials in Sweden

About this study

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.

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.

Read the 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

Being tested
Sirolimus/tacrolimus, cyclosporine/methotrexate
Keywords
GVHD, tacrolimus, sirolimus, cyclosporine, allogeneic, stem cell transplantation, Relapse-free survival
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sirolimus/tacrolimusDrug

    Standard GVHD prophylaxis

  • cyclosporine/methotrexateDrug

    Standard GVHD prophylaxis

Study groups in NCT00993343
Study groupRoleWhat they receive
Cyclosporine + MethotreaxteActive comparatorNot described
Receives: Drug: cyclosporine/methotrexate
sirolimus + tacrolimusActive comparatorNot described
Receives: Drug: Sirolimus/tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary endpoint is grade II-IV acute GVHD

    Measured: One year

Secondary outcomes (2)

  1. Relapse-free survival

    Measured: 2 years

  2. Survival

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2009 (estimated)
  2. Study startSep 2007
  3. Primary completionFeb 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
215 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00993343
Sponsor's protocol ID
070101
Status last verified
Apr 2015
First submitted
9 Oct 2009
Last updated
14 Apr 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30710687

  • 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.

    PubMed 27662016

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sirolimus/tacrolimus and cyclosporine/methotrexate in people with Graft-versus-host Disease and Survival, run by Karolinska Institutet at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary endpoint is grade II-IV acute GVHD (time frame: One year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00993343, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2015.

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