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
methotrexate
+ sirolimus
+ tacrolimus
Blood Protein Disorders+65
+ Bone Marrow Diseases
+ Cardiovascular Diseases
Supportive Care Study
Summary
Study start date: June 1, 2003
Actual date on which the first participant was enrolled.OBJECTIVES: Primary 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. Secondary 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Supportive Care Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: Age Per primary treatment protocol Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic SGOT and SGPT ≤ 2.0 times upper limit of normal Bilirubin normal Hepatitis B and C virus negative Renal Creatinine clearance ≥ 70 mL/min Cardiovascular No cardiac insufficiency requiring treatment No coronary artery disease Pulmonary 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 Other 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 PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No concurrent T-cell depleted transplantations Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery Not specified Other No concurrent grapefruit juice No concurrent voriconazole
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Fred Hutchinson Cancer Research Center
Seattle, United StatesOpen Fred Hutchinson Cancer Research Center in Google Maps