Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia
24 de enero de 2018 actualizado por: The Cleveland Clinic
A Phase II Study of Gemcitabine/ Mitoxantrone in Patients With Acute Myeloid Leukemia in First Relapse
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving gemcitabine together with mitoxantrone works in treating patients with relapsed acute myeloid leukemia.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the complete response (CR) rate (CR and incomplete blood count recovery (CRi)) of patients with acute myeloid leukemia in first relapse treated with gemcitabine hydrochloride and mitoxantrone hydrochloride.
Secondary
- Evaluate disease free and overall survival of patients with acute myeloid leukemia in first relapse treated with this particular chemotherapy regimen.
- Assess hematologic and non-hematologic toxicity associated with this regimen.
- Assess laboratory correlates of drug resistance in patients with relapsed acute myeloid leukemia.
- Assess the percentage of patients receiving subsequent bone marrow transplantation.
OUTLINE: This is an open-label, multicenter study.
Patients receive gemcitabine hydrochloride IV over 12 hours on day 1 and mitoxantrone hydrochloride IV over 30-60 minutes on days 1, 2, and 3. After completion of a single course of therapy, patients who achieve a complete response may receive 1 additional course of therapy at the discretion of the treating physician.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Tipo de estudio
Intervencionista
Inscripción (Actual)
24
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke Comprehensive Cancer Center
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic Taussig Cancer Center
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
DISEASE CHARACTERISTICS:
Bone marrow examination or peripheral blood analysis confirming active acute myeloid leukemia by WHO criteria
- No M3 acute myeloid leukemia
- Not a candidate for allogenic bone marrow transplantation
Patient must be in first relapse after having received induction chemotherapy
- Received 1 or 2 courses with remission lasting at least 1 month
- Patients with chloromas or leukemia cutis are eligible
- No evidence of leptomeningeal involvement
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Liver enzymes (total bilirubin, aspartate aminotransferase (AST) and ALT) ≤ 2.5 times the upper limits of normal
- Liver enzymes ≥ 2.5 are acceptable if physician documents that it is secondary to the disease
- Serum creatinine ≤ 3 mg/dL
- No poorly controlled medical conditions that would seriously complicate compliance with this study
- No other active primary malignancy other than carcinoma in situ of the cervix or basal cell carcinoma of the skin
- No New York Heart Association grade III or IV cardiac problems, defined as congestive heart failure or myocardial infarction within 6 months prior to start of study
- Pregnant or nursing women are ineligible
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study participation
- No documented history of human immunodeficiency virus (HIV) infection
- No history of chronic liver disease
- Ejection fraction ≥ 45%
- No significant history of non-compliance to medical regimens or inability to give reliable informed consent
PRIOR CONCURRENT THERAPY:
- Previous treatment related toxicities should be resolved to grade 1 or better
- No other investigational agents within 14 days prior to the start of study
- No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to start of study
- No major surgery within 2 weeks prior to start of study
- At least two weeks must have elapsed since the conclusion of radiation therapy and the start of gemcitabine hydrochloride, provided the acute effects of radiation treatment have been resolved
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿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: Gemcitabine + Mitoxantrone
Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3.
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10 mg/m2/ min IV for 12 hours
Otros nombres:
12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3
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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Complete Response Rate
Periodo de tiempo: 4 Weeks
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Assumptions/ hypothesis: A Complete Response (CR) rate of 30% or less is unacceptable, and 50% or more is promising.
A two-stage design will be used.
Initially, 18 patients will be enrolled.
If 5 or fewer achieve CR, the study will be stopped.
Otherwise, an additional 22 patients will be accrued.
Accrual was not halted while follow-up of the first 18 evaluable patients was under way.
Therefore, 24 patients were enrolled.
Four weeks is anticipated for observation for response.
Only 5 patients (21%) achieved a CR and therefore, the study was terminated.
Since response was assessed using the International Working Group criteria, a complete response was determined by Morphologic complete remission: A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL, a cytogenic CR and a morphologic CR with incomplete blood count recovery (CRi).
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4 Weeks
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Duration of the First Complete Response
Periodo de tiempo: After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
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After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Disease-free and Overall Survival
Periodo de tiempo: After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
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After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
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Laboratory Correlates: Immunohistochemistry
Periodo de tiempo: Baseline
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Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.
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Baseline
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White Blood Cell Count at Time of Relapse
Periodo de tiempo: After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.
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After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.
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Percentage of Patients Making it to Bone Marrow Transplant.
Periodo de tiempo: After completion of protocol therapy
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Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.
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After completion of protocol therapy
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de enero de 2006
Finalización primaria (Actual)
1 de agosto de 2010
Finalización del estudio (Actual)
1 de julio de 2011
Fechas de registro del estudio
Enviado por primera vez
20 de diciembre de 2005
Primero enviado que cumplió con los criterios de control de calidad
20 de diciembre de 2005
Publicado por primera vez (Estimar)
22 de diciembre de 2005
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
22 de febrero de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
24 de enero de 2018
Última verificación
1 de agosto de 2015
Más información
Términos relacionados con este estudio
Palabras clave
- leucemia mieloide aguda en adultos con anomalías 11q23 (MLL)
- leucemia mieloide aguda en adultos con inv(16)(p13;q22)
- leucemia mieloide aguda en adultos con t(16;16)(p13;q22)
- leucemia mieloide aguda en adultos con t(8;21)(q22;q22)
- leucemia mieloide aguda recurrente en adultos
- leucemia megacarioblástica aguda del adulto (M7)
- adulto leucemia mieloide mínimamente diferenciada aguda (M0)
- leucemia monoblástica aguda del adulto (M5a)
- leucemia monocítica aguda del adulto (M5b)
- leucemia mieloblástica aguda del adulto con maduración (M2)
- leucemia mieloblástica aguda del adulto sin maduración (M1)
- leucemia mielomonocítica aguda del adulto (M4)
- eritroleucemia del adulto (M6a)
- leucemia eritroide pura del adulto (M6b)
Términos MeSH relevantes adicionales
- Neoplasias por tipo histológico
- Neoplasias
- Leucemia
- Leucemia Mieloide
- Leucemia Mieloide Aguda
- 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
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Gemcitabina
- Mitoxantrona
Otros números de identificación del estudio
- CASE-CCF-7725 (Otro identificador: Cleveland Clinic)
- P30CA043703 (Subvención/contrato del NIH de EE. UU.)
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