Sirolimus, Tacrolimus, and Methotrexate in Preventing Acute Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplantation

This study has been completed.
Information provided by:
Fred Hutchinson Cancer Research Center Identifier:
First received: August 4, 2004
Last updated: July 13, 2011
Last verified: July 2011

RATIONALE: Sirolimus, tacrolimus, and methotrexate may be effective in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation.

PURPOSE: This phase I/II trial is studying the side effects of sirolimus when given together with tacrolimus and methotrexate and to see how well they work in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplantation for hematologic cancer.

Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Drug: methotrexate
Drug: sirolimus
Drug: tacrolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase I/II Study of Sirolimus in Addition to Tacrolimus and Methotrexate for the Prevention of Acute-Graft-Versus-Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplantation From Unrelated Donors

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Hypereosinophilic Syndrome Acute Lymphoblastic Leukemia Lymphoma, Small Cleaved-cell, Diffuse B-cell Lymphomas Lymphosarcoma Mantle Cell Lymphoma Multiple Myeloma Leukemia, Myeloid Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Chronic Myeloproliferative Disorders Myelodysplastic Syndromes Follicular Lymphoma Acute Myeloid Leukemia, Adult Chronic Myeloid Leukemia Mycosis Fungoides Sezary Syndrome Cutaneous T-cell Lymphoma Myelofibrosis Hodgkin Lymphoma Homologous Wasting Disease Myelodysplastic/myeloproliferative Disease Juvenile Myelomonocytic Leukemia Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Burkitt Lymphoma Hairy Cell Leukemia Lymphoma, Large-cell Lymphoblastic Lymphoma Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Acute Myeloid Leukemia, Childhood Chronic Neutrophilic Leukemia Small Non-cleaved Cell Lymphoma Hodgkin Lymphoma, Childhood Acute Graft Versus Host Disease Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Study Start Date: June 2003
Study Completion Date: April 2005
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
Detailed Description:



  • Determine the safety and efficacy of sirolimus when administered with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation from unrelated donors.


  • Determine the absorption and pharmacokinetics of sirolimus in patients treated with this regimen.
  • Correlate sirolimus blood concentration with prevention of GVHD or toxicity in patients treated with this regimen.
  • Determine the severity of post-transplantation mucositis in patients treated with this regimen.

OUTLINE: This is a nonrandomized, open-label, pilot study.

Patients receive oral sirolimus once daily on days -3 to 175 and tacrolimus IV continuously beginning on day -3 and continuing until the patient is able to tolerate food and then orally twice daily until day 175. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Treatment continues in the absence of acute graft-vs-host disease or unacceptable toxicity.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3 years.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of hematological malignancy

    • No chronic phase chronic myelogenous leukemia, de novo acute leukemia in first remission, or myelodysplastic syndromes with refractory anemia
  • Scheduled for hematopoietic stem cell transplantation from unrelated donors
  • Currently receiving conditioning regimen comprising cyclosporine and total body radiotherapy (1,200 to 1,350 cGy) or busulfan and cyclosporine
  • Donor must be typed to the highest level of resolution

    • One single non-serologic disparity for A, B, or C alleles allowed provided the disparity is within the third or fourth digit of the allele
    • No mismatch at DRB1 or DQB1



  • Per primary treatment protocol

Performance status

  • Not specified

Life expectancy

  • Not specified


  • Not specified


  • SGOT and SGPT ≤ 2.0 times upper limit of normal
  • Bilirubin normal
  • Hepatitis B and C virus negative


  • Creatinine clearance ≥ 70 mL/min


  • No cardiac insufficiency requiring treatment
  • No coronary artery disease


  • No acute pulmonary infection by chest x-ray
  • No severe hypoxemia with pO_2 < 70 mm Hg AND DLCO < 70% of predicted
  • No mild hypoxemia with pO_2 < 80 mm Hg AND DLCO < 60% of predicted


  • Not pregnant or nursing
  • Negative pregnancy test
  • HIV negative
  • No active systemic infection
  • No known hypersensitivity to macrolide antibiotics (e.g., erythromycin, azithromycin, or clarithromycin)
  • No prior intolerance or unresponsiveness to sirolimus


Biologic therapy

  • See Disease Characteristics
  • No concurrent T-cell depleted transplantations


  • See Disease Characteristics

Endocrine therapy

  • Not specified


  • See Disease Characteristics


  • Not specified


  • No concurrent grapefruit juice
  • No concurrent voriconazole
  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 identifier: NCT00089037

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Principal Investigator: Hans-Peter Kiem, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Kiem, Hans-Peter, Fred Hutchinson Cancer Research Center Identifier: NCT00089037     History of Changes
Other Study ID Numbers: 1811.00, FHCRC-1811.00, CDR0000378004
Study First Received: August 4, 2004
Last Updated: July 13, 2011
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
graft versus host disease
accelerated phase chronic myelogenous leukemia
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
de novo myelodysplastic syndromes
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Graft vs Host Disease
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Pathologic Processes
Everolimus processed this record on October 19, 2014