A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) Versus Antithymocyte Globulin (ATG) to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)
Colección de datos
Enfermedades de la Médula Ósea+1
+ Enfermedades hemáticas y linfáticas
+ Enfermedades Hematológicas
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de noviembre de 2003
Fecha en la que se inscribió al primer participante.Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG), however, nonresponse and relapse continues to be a problem. Why some patients do not respond initially or others respond and then relapse is unclear. Autoreactive T cells may be resistant to the effect of ATG/CsA (nonresponders), while in others residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel, less toxic immunosuppressive regimens that increase response rates and hematologic recovery and decrease relapse rates are needed. One such novel therapy, Daclizumab, a humanized anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb), acts against activated lymphocytes, thus sharing an important mechanism of action with ATG. The mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals (every 2 weeks). Treatments with ATG alone and CsA alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS. Our experience suggests that ATG rather than CSA is the more effective agent inducing hematological responses in susceptible MDS patients and that certain variables including the patient's age, whether or not they were HLA DR15, and days of red cell transfusion dependence prior to treatment were predictive of response. We therefore propose this randomized phase II study to evaluate and compare a new immunosuppressive therapy, Daclizumab, with antithymocyte globulin (ATG) to treat the cytopenia of MDS in a population of subjects with intermediate or high predicted probability of response.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 132 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
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
INCLUSION CRITERIA: MDS of RA, RARS \& RAEB sub-types including those previously treated with chemotherapy or experimental agents such as retinoids, Vitamin D, and growth factors Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months OR thrombocytopenia (platelet count less than 50000/ul) OR neutropenia (absolute neutrophil count less than 500/ul). Off all other treatments (except G-CSF, and transfusion support and related medications) for at least four weeks. G-CSF can be used before, during and after the protocol treatment for patients with documented neutropenia (less than 500/Ul) as long as they meet the criteria for anemia and/or thrombocytopenia as stated above. ECOG performance status less than or equal to 2 High or intermediate predicted probability of response EXCLUSION CRITERIA: MDS of FAB sub-group chronic myelomonocytic leukemia (CMML) Transformation to acute leukemia (FAB sub-group RAEB-T, ie, greater than 20% blasts in marrow aspirate) Hypoplastic marrow without one major or two minor criteria Treatment with growth factors (except for G-CSF) or cyclosporine within 4 weeks prior to entry to protocol Recent or current treatment (24 hours wash out period) with the herbal supplement Echinacea purpurea or Usnea barbata (Old Man's Beard) ECOG performance status of greater than 2 Active uncontrolled infection (chronic or current clinically significant infection, including hepatitis B or C virus infection) Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential Patients for whom bone marrow transplant is indicated as standard therapy (age less than fifty-five with a fully-matched sibling donor) Age less than 18 years Not able to understand the investigational nature of the study or give informed consent HIV positive patients Active malignant disease (excluding basal cell carcinoma) Serum creatinine greater than 2mg/dl Patients who are moribund or patients with concurrent hepatic, renal, cardiac, metabolic, or any disease of such severity that death within 3 months is likely Low predicted probability of response
Centros del Estudio
Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.Este estudio tiene una ubicación
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, United StatesAbrir National Heart, Lung and Blood Institute (NHLBI) en Google Maps