- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01729845
Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study
Descripción general del estudio
Estado
Condiciones
Descripción detallada
PRIMARY OBJECTIVES:
I. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with relapsed/refractory acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. Determine, within the limits of a Phase 1/2 study, disease response and duration of remission.
II. Identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and/or gene expression changes) associated with treatment responses.
OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study.
Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.
After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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-
Washington
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Kennewick, Washington, Estados Unidos, 99336
- Kadlec Clinic Hematology and Oncology
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Kirkland, Washington, Estados Unidos, 98033
- EvergreenHealth Medical Center
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutch/University of Washington Cancer Consortium
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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:
- Prior diagnosis of "high-risk" myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible
- Relapsed/persistent disease according to standard criteria requiring salvage therapy; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
- Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents
- Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model
- Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved
- May have previously received monotherapy with demethylating agents for MDS or AML
- May have previously received chemotherapy with MEC for MDS or AML
- Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment
- Bilirubin =< 2 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 7 days prior to study day 1)
- Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to study day 1)
- Left ventricular ejection fraction >= 40%, assessed within 3 months prior to study day 1, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographical suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal
- Women of childbearing potential and men must agree to use adequate contraception
- Provide written informed consent
Exclusion Criteria:
- Refractory/relapsing myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
- Concomitant illness associated with a likely survival of < 1 year
- Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible
- Known hypersensitivity to any study drug
- Pregnancy or lactation
- Patients may not be receiving any other investigational agents
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 |
---|---|
Experimental: Treatment (decitabine, MEC)
Patients receive decitabine IV on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. |
Estudios correlativos
Dado IV
Otros nombres:
Dado IV
Otros nombres:
Dado IV
Otros nombres:
Dado IV
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Most Efficacious and Tolerated Dosage of Decitabine (Period 1)
Periodo de tiempo: through day 45
|
MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities.
MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
|
through day 45
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Remission Rate Including CR and CRp
Periodo de tiempo: Up to 5 years
|
Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups: Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1. |
Up to 5 years
|
Duration of Relapse-free Survival (for Patients Achieving CR or CRp)
Periodo de tiempo: Up to 5 years
|
Categorized according to criteria recommended by International Working Groups.
|
Up to 5 years
|
Overall Survival
Periodo de tiempo: Up to 5 years
|
Survival measured as of day of last contact.
Categorized according to criteria recommended by International Working Groups.
|
Up to 5 years
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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 (Actual)
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 por tipo histológico
- Neoplasias
- Enfermedad
- Enfermedades de la médula ósea
- Enfermedades hematológicas
- Condiciones precancerosas
- Síndrome
- Síndromes mielodisplásicos
- Leucemia
- Leucemia Mieloide
- Leucemia Mieloide Aguda
- Preleucemia
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes del sistema nervioso periférico
- Agentes Antivirales
- Inhibidores de enzimas
- Analgésicos
- Agentes del sistema sensorial
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Agentes dermatológicos
- Agentes queratolíticos
- Etopósido
- Fosfato de etopósido
- Decitabina
- Podofilotoxina
- Citarabina
- Mitoxantrona
Otros números de identificación del estudio
- 2652.00 (Otro identificador: Fred Hutch/University of Washington Cancer Consortium)
- P30CA015704 (Subvención/contrato del NIH de EE. UU.)
- 2652
- NCI-2012-02224 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- FH#2652
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. .
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