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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.
National Cancer Institute (NCI)
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:

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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
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
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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
National Cancer Institute (NCI)
Principal Investigator: Hans-Peter Kiem, MD Fred Hutchinson Cancer Research Center
  More Information

Responsible Party: Kiem, Hans-Peter, Fred Hutchinson Cancer Research Center Identifier: NCT00089037     History of Changes
Other Study ID Numbers: 1811.00
CDR0000378004 ( Registry Identifier: PDQ )
Study First Received: August 4, 2004
Last Updated: July 13, 2011

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
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Methotrexate processed this record on May 25, 2017