Clinical Trial: 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 is currently recruiting patients.

Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)


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 Treatment or Intervention Phase
childhood Hodgkin's lymphoma
childhood non-Hodgkin's lymphoma
Graft Versus Host Disease
hematopoietic and lymphoid cancer
 Drug: methotrexate
 Drug: sirolimus
 Drug: tacrolimus
 Procedure: biological response modifier therapy
 Procedure: complications of therapy assessment/management
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: supportive care/therapy
Phase I
Phase II

MedlinePlus related topics:  Hodgkin's Disease;   Immune System and Disorders;   Lymphoma

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I/II Pilot Study of Sirolimus, Tacrolimus, and Methotrexate for the Prevention of Acute Graft-Versus-Host Disease in Patients With Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation From Unrelated Donors

Further Study Details: 



  • 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




  • 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


  • 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

Location and Contact Information

      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
Hans-Peter Kiem, MD  206-667-4425 

Study chairs or principal investigators

Hans-Peter Kiem, MD,  Principal Investigator,  Fred Hutchinson Cancer Research Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000378004; FHCRC-1811.00; NCT00089037
Record last reviewed:  July 2004
Last Updated:  February 15, 2005
Record first received:  August 4, 2004 Identifier:  NCT00089037
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005