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
Colección de datos
Trastornos de las Proteínas Sanguíneas+22
+ Enfermedades Cardiovasculares
+ Enfermedad
Estudio de Cuidados de Apoyo
Resumen
Fecha de inicio: 1 de junio de 2003
Fecha en la que se inscribió al primer participante.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.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Estudio de Cuidados de Apoyo
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
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
Centros del Estudio
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