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.
Sponsor:
Fred Hutchinson Cancer Research Center
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00089037
First received: August 4, 2004
Last updated: July 13, 2011
Last verified: July 2011
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Purpose
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 Leukemia Lymphoma 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:
Genetics Home Reference related topics:
familial acute myeloid leukemia with mutated CEBPA
mycosis fungoides
Sézary syndrome
MedlinePlus related topics:
Acute Myeloid Leukemia
Cancer
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Drug Information available for:
Methotrexate
Methotrexate sodium
Sirolimus
Tacrolimus
Everolimus
Temsirolimus
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) |
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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00089037
Locations
| United States, Washington | |
| Fred Hutchinson Cancer Research Center | |
| Seattle, Washington, United States, 98109-1024 | |
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
| 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 |
| ClinicalTrials.gov 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:
|
Neoplasms Graft vs Host Disease Leukemia Lymphoma Lymphoma, Non-Hodgkin Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Myelodysplastic Syndromes Preleukemia Myeloproliferative Disorders Lymphoma, Large-Cell, Immunoblastic Myelodysplastic-Myeloproliferative Diseases Immune System Diseases Neoplasms by Histologic Type |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Bone Marrow Diseases Precancerous Conditions Methotrexate Sirolimus Everolimus |
ClinicalTrials.gov processed this record on May 23, 2013