- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00384956
A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.
The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:
- Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion
- Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
- Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL.
- ECOG performance status of 0-2.
- Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
- Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).
- Life expectancy of at least 12 weeks.
- Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities.
- Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
- Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial.
- Men must be willing to avoid fathering a new child while receiving therapy with azacitidine.
- ≥18 years, no upper age limit
- Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation.
Exclusion Criteria:
- Known CNS leukemia.
- Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
- Known or suspected hypersensitivity to azacitidine or mannitol.
- Receiving any other investigational agents within 30 days of first dose of study drug.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Known positive serology for HIV.
- Had radiotherapy within 14 days prior to study enrollment.
- Known presence of hepatic tumors.
- <18 years of age
- Exclude women who are pregnant or breast feeding.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Azacitidine
Azacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle.
Patients that do not respond after two cycles will have the dose increased to 100 mg/m2.
Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle.
Individuals who demonstrate a loss of response will resume 28 day cycles.
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Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Rate of Complete Remission (CR) and Partial Remission (PR)
Periodo de tiempo: After 4 cycles of therapy (up to 112 days after start of treatment)
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Defined according to the modified International Working Group (IWG) (2006) response criteria for myelodysplasia: CR=bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L. Residual dysplasia was allowed. PR= All of the CR criteria if abnormal before treatment except: bone marrow blasts decreased by ≥50% over pretreatment but still >5%. |
After 4 cycles of therapy (up to 112 days after start of treatment)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Rate of Hematologic Improvement
Periodo de tiempo: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
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International Working Group (IWG) for Myelodysplasia (MDS).
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4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
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Rate of Transfusion Independence
Periodo de tiempo: 4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
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4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]
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Rate of Cytogenetic Response
Periodo de tiempo: 2 years after first dose of study drug or until participant is lost to follow-up or dies
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2 years after first dose of study drug or until participant is lost to follow-up or dies
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Rate of Overall Survival
Periodo de tiempo: 2 years after first dose of study drug or until participant is lost to follow-up or dies
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Overall survival is defined as the date of first dose of study drug to the date of death from any cause.
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2 years after first dose of study drug or until participant is lost to follow-up or dies
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Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.
Periodo de tiempo: 2 years after first dose of study drug or until participant is lost to follow-up or dies
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2 years after first dose of study drug or until participant is lost to follow-up or dies
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Neoplasias
- Enfermedad
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Condiciones precancerosas
- Síndrome
- Síndromes mielodisplásicos
- Preleucemia
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Azacitidina
Otros números de identificación del estudio
- 06-0585
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Azacitidina
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Ohio State University Comprehensive Cancer CenterMillennium Pharmaceuticals, Inc.; Celgene CorporationTerminadoSíndromes mielodisplásicos | Leucemia | Neoplasias mielodisplásicas/mieloproliferativasEstados Unidos