Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
21 de abril de 2016 actualizado por: Teva Branded Pharmaceutical Products R&D, Inc.
An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
The primary objective of phase 1 of this study is to establish the recommended phase II dose (RP2D).
The primary objective of phase 2 of this study is to evaluate the safety and efficacy of bendamustine at the recommended pediatric dose for the treatment of pediatric patients with relapsed or refractory acute leukemia.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
43
Fase
- Fase 2
- Fase 1
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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Herston, Australia
- Teva Investigational Site 300
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Parkville, Australia
- Teva Investigational Site 301
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Randwick, Australia
- Teva Investigational Site 302
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Minsk, Bielorrusia
- Teva Investigational Site 520
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Barretos-SP, Brasil
- Teva Investigational Site 615
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Caxias do Sul, Brasil
- Teva Investigational Site 616
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Curitiba-PR, Brasil
- Teva Investigational Site 613
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Porto Alegre, Brasil
- Teva Investigational Site 612
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Porto Alegre, Brasil
- Teva Investigational Site 614
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Sao Paulo, Brasil
- Teva Investigational Site 610
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Sao Paulo, Brasil
- Teva Investigational Site 611
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Sao Paulo-SP, Brasil
- Teva Investigational Site 617
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Toronto, Canadá
- Teva Investigational Site 100
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Seoul, Corea, república de
- Teva Investigational Site 330
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Seoul, Corea, república de
- Teva Investigational Site 331
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Seoul, Corea, república de
- Teva Investigational Site 332
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Seoul, Corea, república de
- Teva Investigational Site 333
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California
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Orange, California, Estados Unidos
- Teva Investigational Site 17
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San Diego, California, Estados Unidos
- Teva Investigational Site 12
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Florida
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St. Petersburg, Florida, Estados Unidos
- Teva Investigational Site 10
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Maryland
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Baltimore, Maryland, Estados Unidos
- Teva Investigational Site 8
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Massachusetts
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Boston, Massachusetts, Estados Unidos
- Teva Investigational Site 16
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Michigan
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Detroit, Michigan, Estados Unidos
- Teva Investigational Site 9
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Mississippi
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Jackson, Mississippi, Estados Unidos
- Teva Investigational Site 1
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Missouri
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Kansas City, Missouri, Estados Unidos
- Teva Investigational Site 5
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St. Louis, Missouri, Estados Unidos
- Teva Investigational Site 14
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New York
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New York, New York, Estados Unidos
- Teva Investigational Site 15
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Oregon
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Portland, Oregon, Estados Unidos
- Teva Investigational Site 18
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos
- Teva Investigational Site 11
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Philadelphia, Pennsylvania, Estados Unidos
- Teva Investigational Site 7
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Tennessee
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Memphis, Tennessee, Estados Unidos
- Teva Investigational Site 19
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Texas
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Dallas, Texas, Estados Unidos
- Teva Investigational Site 3
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Fort Worth, Texas, Estados Unidos
- Teva Investigational Site 4
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Houston, Texas, Estados Unidos
- Teva Investigational Site 13
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Washington
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Seattle, Washington, Estados Unidos
- Teva Investigational Site 2
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos
- Teva Investigational Site 6
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Moscow, Federación Rusa
- Teva Investigational Site 511
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St. Petersburg, Federación Rusa
- Teva Investigational Site 510
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Jerusalem, Israel
- Teva Investigational Site 501
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Petach Tikva, Israel
- Teva Investigational Site 503
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Ramat Gan, Israel
- Teva Investigational Site 502
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Guadalajara, México
- Teva Investigational Site 603
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Mexico City, México
- Teva Investigational Site 600
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Mexico City, México
- Teva Investigational Site 601
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Monterrey, México
- Teva Investigational Site 602
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Auckland, Nueva Zelanda
- Teva Investigational Site 303
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Bialystok, Polonia
- Teva Investigational Site 531
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Lublin, Polonia
- Teva Investigational Site 530
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Warszawa, Polonia
- Teva Investigational Site 532
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Singapore, Singapur
- Teva Investigational Site 320
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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
1 año a 20 años (Niño, Adulto)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Key Inclusion Criteria:
- The patient has histologically proven acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) that has relapsed or is refractory to the last regimen, and the patient is without alternative curative therapy.
- The patient's last myelosuppression therapy ended at least 2 weeks before the first dose of study drug.
- Nonhematologic acute toxic effects of prior therapy have resolved to grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
- The patient has adequate liver function with bilirubin values less than or equal to 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values less than or equal to 5 times the age-appropriate ULN.
- The patient has adequate renal function with serum creatinine values less than 2 times ULN.
- The patient has Karnofsky or Lansky performance status of 60 or greater. Patients older than 16 years of age will be scored according to the Karnofsky scale and patients 16 years of age or younger will be scored according to the Lansky scale.
- The patient may have had hematopoietic stem cell transplantation.
- Women of childbearing potential (not surgically sterile) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
- Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
- The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.
Key Exclusion Criteria:
- The patient has any active, uncontrolled systemic infection, severe concurrent disease, or symptomatic untreated central nervous system (CNS) involvement.
- The patient has evidence of active graft versus host disease.
- The patient has a known human immunodeficiency virus (HIV) infection.
- The patient has active hepatitis B or hepatitis C infection.
- The patient is a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study immediately.
- The patient has any serious uncontrolled medical or psychological disorder that would impair the ability of the patient to receive study drug.
- The patient has any condition that places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.
- The patient has received any other investigational agent within 30 days of study entry.
- The patient has known hypersensitivity to bendamustine or mannitol.
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: Bendamustine
Bendamustine 90 or 120 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Recommended Phase II Dose (RP2D) of Bendamustine
Periodo de tiempo: Induction Cycle (21- to 35-day cycle)
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RP2D was determined by a traditional 3+3 dose escalation design, with the following restrictions: only doses of 60, 90, 120, and 150 mg/m^2 were explored, and escalation to 150 mg/m^2 would only occur if the 120 mg/m^2 dose was deemed safe and pharmacokinetic data indicate subtherapeutic exposure as compared with adults.
The first cohort was administered bendamustine at the 90 mg/m^2 dose; de-escalation to the 60 mg/m^2 dose would only occur if the starting dose led to dose-limiting toxicity (DLT) in 2 or more participants.
A DLT was defined as any study drug-related nonhematologic adverse event (AE) that was grade 4 for toxicity by National Cancer Institute's Common Toxicity Criteria for AEs, version 4. In addition, grade 3 or above allergic reaction or skin rash were considered DLTs.
Hematologic AEs were not considered DLTs.
The dose level at which at least 2 of 3 or 2 of 6 participants had a DLT was considered as exceeding the RP2D.
The RP2D was the dose 1 step below that level.
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Induction Cycle (21- to 35-day cycle)
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Overall Response Rate (ORR)
Periodo de tiempo: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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ORR was calculated as follows: number of participants in the primary analysis set achieving a best overall response of complete remission without platelet recovery (CRp) or complete remission (CR), divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A CR required no evidence of circulating blasts or extramedullary disease, an M1 marrow (≤ 5% bone marrow blasts), and recovery of peripheral counts (platelets ≥ 100 × 10^9/L and absolute neutrophil count ≥ 1.0 × 10^9/L).
A CR without platelet recovery (CRp) required all of the criteria for a CR with the exception of platelet recovery.
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Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Best Overall Tumor Response Rate
Periodo de tiempo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Best Overall Tumor Response Rate, by Phase
Periodo de tiempo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Duration of Response (DOR)
Periodo de tiempo: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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DOR was determined for the participants with CR or CRp in the primary analysis set, defined as the time from first achieving remission to the time when progression was diagnosed, the participant died, or the participant started receiving new antineoplastic therapy.
Data from participants who do not progress were censored at the last valid assessments.
Median DOR and its 95% confidence interval was determined based on the Kaplan-Meier method.
Data from participants who received a transplant were censored at the time of the transplant.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Periodo de tiempo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Periodo de tiempo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until the Last Measurable Plasma Concentration (AUC0-t) for Bendamustine and Its Metabolites (M3 and M4)
Periodo de tiempo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until 24 Hours After Study Drug Administration (AUC0-24) for Bendamustine and Its Metabolites (M3 and M4)
Periodo de tiempo: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2.
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
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 agosto de 2010
Finalización primaria (Actual)
1 de agosto de 2011
Finalización del estudio (Actual)
1 de agosto de 2011
Fechas de registro del estudio
Enviado por primera vez
16 de marzo de 2010
Primero enviado que cumplió con los criterios de control de calidad
16 de marzo de 2010
Publicado por primera vez (Estimar)
18 de marzo de 2010
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
23 de mayo de 2016
Última actualización enviada que cumplió con los criterios de control de calidad
21 de abril de 2016
Última verificación
1 de abril de 2016
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- C18083/2046
- 2010-020768-40 (Número EudraCT)
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. .