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- Ensayo clínico NCT01900509
Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies
A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies
Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. This drug is approved by the Food and Drug Administration (FDA) for the treatment of other cancers in adults that are similar to those being studied in the research trial.
PRIMARY OBJECTIVES
- To establish the maximum tolerated dose (MTD) of bendamustine in combination with clofarabine and etoposide in pediatric participants with hematologic malignancies.
- To characterize the safety profile and dose-limiting toxicities (DLTs) of bendamustine in combination with clofarabine and etoposide.
SECONDARY OBJECTIVES
- To estimate event-free survival at 4 months.
- To estimate minimal residual disease (MRD) levels present at end of each cycle of therapy in participants with leukemia.
- To characterize the pharmacokinetic profile of bendamustine in the proposed regimen.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Bendamustine will be combined with clofarabine and etoposide in a five-day cycle. Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine.
If the participant does not develop progressive disease or a dose-limiting toxicity (DLT) during the first cycle, a second cycle may be administered as a bridge to transplant. Each cycle lasts 21-28 days (or until count recovery).
Concomitant intrathecal therapy can be given at the investigator's discretion, but not on the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate, hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two weeks for participants with CNS1 disease. Leucovorin may be given according to institutional guidelines.
The intent of this study design is for all participants to receive and complete one course of therapy. Participants who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from protocol treatment.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38105
- St. Jude Children's Research Hospital
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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
- Participants with Hodgkin or Non-Hodgkin lymphoma must meet one of the following criteria: (a) Relapsing disease in 2nd or greater relapse and measurable disease, or (b) Refractory disease failing to achieve complete remission (CR) with > 2 induction or re-induction attempts.
- Participant with acute leukemia must meet one of the following criteria: (a) Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute biphenotypic leukemia in 2nd or greater relapse; or (b) Refractory ALL, AML, or acute biphenotypic leukemia failing to achieve CR with ≥ 2 induction or re-induction attempts.
- Participant with leukemia has M2 or M3 marrow at the time of enrollment. Participant with M2 marrow must have definite cytogenetic, molecular, or immunophenotypic evidence of recurrent/refractory disease.
- Age is ≤ 21 years (participant has not yet reached 22nd birthday).
- Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.
- There are no known contra-indications to any of the planned agents used in this protocol. Etoposide may be substituted by etoposide phosphate (etopophos) if the patient has a history of hypersensitivity reaction to etoposide
- Adequate renal function defined as glomerular filtration rate > 60 cc/min/1.73m2, or normal serum creatinine based on age.
- Adequate hepatic function: (a) Direct bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.4 mg/dl, and (b) AST and ALT ≤ 5 x ULN for age.
- Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.
- Lymphoma participants without bone marrow involvement must have: (a) Absolute neutrophil count (ANC) ≥ 1,000/µL, and (b) Platelet count > 50,000/mm^3 (without transfusion support). [Note: these criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement.]
Participant must have recovered from the acute side effects of all prior anti-cancer therapy, and :
- At least 2 weeks have elapsed since prior systemic cytotoxic chemotherapy (except intrathecal chemotherapy, and/or low dose maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids), and
- At least 4 weeks have elapsed since treatment with an investigational agent or antibody-based therapy, if applicable, and
- If the participant received a prior allogeneic hematopoietic stem cell transplantation (HSCT), at least 3 months have elapsed and there is no evidence of active graft-versus-host disease (GVHD), participant has discontinued immunosuppression, and there is no history of veno-occlusive disease.
EXCLUSION CRITERIA
- Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness.
- Isolated extramedullary disease (leukemia).
- Primary CNS lymphoma.
- Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment).
- Known HIV or active hepatitis B or C infection.
- Known hypersensitivity to bendamustine or mannitol.
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: Treatment
All participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone. |
Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.
Otros nombres:
Route of administration: IV days 1-5.
Otros nombres:
Route of administration: IV days 1-5.
Otros nombres:
Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.
Otros nombres:
Route of administration: three times daily orally (by mouth), days 1-5.
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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Maximum tolerated dose
Periodo de tiempo: Continually throughout the study (up to 3 months)
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Establish MTD of bendamustine in combination with clofarabine and etoposide.
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Continually throughout the study (up to 3 months)
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Dose limiting toxicities
Periodo de tiempo: Continually throughout the study (up to 3 months)
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Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide
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Continually throughout the study (up to 3 months)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Event free survival
Periodo de tiempo: 4 months after the start of therapy for the last patient enrolled on the study
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Event-free survival (EFS) time will be calculated from on therapy to any kind of failure or to last contact date for participants who are alive without any failure at the last contact date.
The time to EFS will be set to 0 for participants who fail to achieve complete remission.
Kaplan-Meier estimates of EFS curves will be computed, along with estimates of standard errors by the method of Peto.
Four month EFS, as well as longer term survival rates (6 month and 1 year) will be estimated with 95% confidence intervals.
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4 months after the start of therapy for the last patient enrolled on the study
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Proportion of leukemia participants with positive minimal residual disease
Periodo de tiempo: At end of each cycle of chemotherapy (approximately at 1 month and 2 months)
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The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
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At end of each cycle of chemotherapy (approximately at 1 month and 2 months)
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Plasma concentration of bendamustine
Periodo de tiempo: Day 1 and day 5 of cycle 1 therapy
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Plasma concentrations of bendamustine will be measured using an established LC-MS/MS assay.
Bendamustine pharmacokinetic parameters such as Cmax, tmax, AUC (0-t), t1/2, and clearance will be estimated using population-based modeling techniques.
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Day 1 and day 5 of cycle 1 therapy
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Colaboradores e Investigadores
Patrocinador
Colaboradores
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 (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Neoplasias por sitio
- Enfermedades hematológicas
- Linfoma
- Neoplasias Hematológicas
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes Autonómicos
- Agentes del sistema nervioso periférico
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Antieméticos
- Agentes Gastrointestinales
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Dexametasona
- Etopósido
- Fosfato de etopósido
- Clofarabina
- Clorhidrato de bendamustina
Otros números de identificación del estudio
- BECHEM
- TEVA ISS (Otro identificador: Teva Pharmaceuticals)
- NCI-2013-01148 (Identificador de registro: NCI Clinical Trial Registration Program)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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 Linfoma de Hodgkin
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National Cancer Institute (NCI)TerminadoLinfoma de Hodgkin en adultos recidivante | Linfoma de Hodgkin en adultos en estadio III | Linfoma de Hodgkin en adultos en estadio IV | Linfoma de Hodgkin infantil recidivante/refractario | Linfoma de Hodgkin infantil en estadio III | Linfoma de Hodgkin infantil en estadio IV | Linfoma de Hodgkin... y otras condicionesEstados Unidos
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminadoLinfoma de Hodgkin recurrente | Linfoma de Hodgkin refractario | Linfoma no Hodgkin de células B refractario | Linfoma no Hodgkin de células T refractario | Linfoma no Hodgkin de células B recurrente | Linfoma no Hodgkin de células T recurrenteEstados Unidos
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University of WashingtonReclutamientoLinfoma de Hodgkin recurrente | Linfoma de Hodgkin refractario | Linfoma no Hodgkin recurrente | Linfoma no Hodgkin refractarioEstados Unidos
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Tomsk National Research Medical Center of the Russian...Uppsala UniversityTerminadoLinfoma de Hodgkin en adultos | Linfoma no Hodgkin en adultosFederación Rusa
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Marker Therapeutics, Inc.ReclutamientoNo linfoma de Hodgkin | Linfoma no Hodgkin en adultos | Linfoma no Hodgkin, refractario | Linfoma no Hodgkin en recaídaEstados Unidos
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Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Activo, no reclutandoLinfoma de Hodgkin en estadio III de Ann Arbor | Linfoma de Hodgkin en estadio IIIA de Ann Arbor | Linfoma de Hodgkin en estadio IIIB de Ann Arbor | Linfoma de Hodgkin en estadio IV de Ann Arbor | Linfoma de Hodgkin en estadio IVA de Ann Arbor | Linfoma de Hodgkin en estadio IVB de Ann Arbor | Linfoma... y otras condicionesEstados Unidos
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Tessa TherapeuticsActivo, no reclutandoLinfoma de Hodgkin en adultos | Enfermedad de Hodgkin Recurrente | Enfermedad de Hodgkin refractario | Enfermedad de Hodgkin, PediátricaEstados Unidos
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Shanghai Zhongshan HospitalReclutamientoLinfoma | Linfoma de Hodgkin | No linfoma de HodgkinPorcelana
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GenmabReclutamientoNo linfoma de Hodgkin | Linfoma de Hodgkin clásicoEstados Unidos, Australia
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ADC Therapeutics S.A.TerminadoLinfoma de Hodgkin | No linfoma de HodgkinEstados Unidos, Reino Unido
Ensayos clínicos sobre Bendamustine
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Medical University of ViennaAún no reclutando
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ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)Terminado