Sirolimus, Tacrolimus, and Methotrexate in Preventing Acute Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplantation
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109-1024 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Hans-Peter Kiem, MD, Fred Hutchinson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1811.00
- FHCRC-1811.00
- CDR0000378004