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Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia

2016年4月21日 更新者：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.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

43

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 以色列
      • Jerusalem、以色列
        • Teva Investigational Site 501
      • Petach Tikva、以色列
        • Teva Investigational Site 503
      • Ramat Gan、以色列
        • Teva Investigational Site 502
  • 俄罗斯联邦
      • Moscow、俄罗斯联邦
        • Teva Investigational Site 511
      • St. Petersburg、俄罗斯联邦
        • Teva Investigational Site 510
  • 加拿大
      • Toronto、加拿大
        • Teva Investigational Site 100
  • 墨西哥
      • Guadalajara、墨西哥
        • Teva Investigational Site 603
      • Mexico City、墨西哥
        • Teva Investigational Site 600
      • Mexico City、墨西哥
        • Teva Investigational Site 601
      • Monterrey、墨西哥
        • Teva Investigational Site 602
  • 大韩民国
      • Seoul、大韩民国
        • Teva Investigational Site 330
      • Seoul、大韩民国
        • Teva Investigational Site 331
      • Seoul、大韩民国
        • Teva Investigational Site 332
      • Seoul、大韩民国
        • Teva Investigational Site 333
  • 巴西
      • Barretos-SP、巴西
        • Teva Investigational Site 615
      • Caxias do Sul、巴西
        • Teva Investigational Site 616
      • Curitiba-PR、巴西
        • Teva Investigational Site 613
      • Porto Alegre、巴西
        • Teva Investigational Site 612
      • Porto Alegre、巴西
        • Teva Investigational Site 614
      • Sao Paulo、巴西
        • Teva Investigational Site 610
      • Sao Paulo、巴西
        • Teva Investigational Site 611
      • Sao Paulo-SP、巴西
        • Teva Investigational Site 617
  • 新加坡
      • Singapore、新加坡
        • Teva Investigational Site 320
  • 新西兰
      • Auckland、新西兰
        • Teva Investigational Site 303
  • 波兰
      • Bialystok、波兰
        • Teva Investigational Site 531
      • Lublin、波兰
        • Teva Investigational Site 530
      • Warszawa、波兰
        • Teva Investigational Site 532
  • 澳大利亚
      • Herston、澳大利亚
        • Teva Investigational Site 300
      • Parkville、澳大利亚
        • Teva Investigational Site 301
      • Randwick、澳大利亚
        • Teva Investigational Site 302
  • 白俄罗斯
      • Minsk、白俄罗斯
        • Teva Investigational Site 520
  • 美国
    • California
      • Orange、California、美国
        • Teva Investigational Site 17
      • San Diego、California、美国
        • Teva Investigational Site 12
    • Florida
      • St. Petersburg、Florida、美国
        • Teva Investigational Site 10
    • Maryland
      • Baltimore、Maryland、美国
        • Teva Investigational Site 8
    • Massachusetts
      • Boston、Massachusetts、美国
        • Teva Investigational Site 16
    • Michigan
      • Detroit、Michigan、美国
        • Teva Investigational Site 9
    • Mississippi
      • Jackson、Mississippi、美国
        • Teva Investigational Site 1
    • Missouri
      • Kansas City、Missouri、美国
        • Teva Investigational Site 5
      • St. Louis、Missouri、美国
        • Teva Investigational Site 14
    • New York
      • New York、New York、美国
        • Teva Investigational Site 15
    • Oregon
      • Portland、Oregon、美国
        • Teva Investigational Site 18
    • Pennsylvania
      • Hershey、Pennsylvania、美国
        • Teva Investigational Site 11
      • Philadelphia、Pennsylvania、美国
        • Teva Investigational Site 7
    • Tennessee
      • Memphis、Tennessee、美国
        • Teva Investigational Site 19
    • Texas
      • Dallas、Texas、美国
        • Teva Investigational Site 3
      • Fort Worth、Texas、美国
        • Teva Investigational Site 4
      • Houston、Texas、美国
        • Teva Investigational Site 13
    • Washington
      • Seattle、Washington、美国
        • Teva Investigational Site 2
    • Wisconsin
      • Milwaukee、Wisconsin、美国
        • Teva Investigational Site 6

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

1年 至 20年 (孩子、成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：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.
药品：苯达莫司汀

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Recommended Phase II Dose (RP2D) of Bendamustine
大体时间：Induction Cycle (21- to 35-day cycle)
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.
Induction Cycle (21- to 35-day cycle)
Overall Response Rate (ORR)
大体时间：Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles

次要结果测量

结果测量
措施说明
大体时间
Best Overall Tumor Response Rate
大体时间：At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Best Overall Tumor Response Rate, by Phase
大体时间：At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Duration of Response (DOR)
大体时间：At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
大体时间：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.
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.
Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
大体时间：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.
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.
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)
大体时间：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.
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.
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)
大体时间：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.
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.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Teva Branded Pharmaceutical Products R&D, Inc.

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2010年8月1日

初级完成 (实际的)

2011年8月1日

研究完成 (实际的)

2011年8月1日

研究注册日期

首次提交

2010年3月16日

首先提交符合 QC 标准的

2010年3月16日

首次发布 (估计)

2010年3月18日

研究记录更新

最后更新发布 (估计)

2016年5月23日

上次提交的符合 QC 标准的更新

2016年4月21日

最后验证

2016年4月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • C18083/2046
  • 2010-020768-40 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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