此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide in Untreated CLL

2016年5月25日 更新者：Arbeitsgemeinschaft medikamentoese Tumortherapie

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Escalating Starting Dose of Lenalidomide and Concomitant Evaluation of Safety and Efficacy

This is a trial in patients with previously untreated CLL. Eligible patients will receive Lenalidomide with a backbone of Fludarabine and Rituximab for 6 therapy cycles. Lenalidomide will be increased by dose steps of 5 mg every cycle in the absence of limiting toxicity. If limiting toxicity ensues the patients will be treated with last tolerable dose for the remainder of the 6 treatment cycles.

The first 5 patients will start with dose level 5 mg Lenalidomide and further escalating dose. After the fifth patient is included in the study, enrolment will be interrupted until this patient has finished his first treatment cycle. A safety board will evaluate the toxicities of the first 5 patients. If there are more than 2 patients experiencing a dose limiting toxicity (DLT) in the first treatment cycle, the starting dose will not be escalated and further 5 patients will be enrolled with a starting dose of 5 mg Lenalidomide. If only 2 or less patients experience a DLT in the first treatment cycle, the next 5 patients will start the treatment with 10 mg Lenalidomide.

The rational for the higher starting doses stems from the lack of tumor lysis or tumor flare toxicity in this combination on the one hand and from the observation that the very slow escalation from 2,5 mg on led to a lack of efficacy in monotherapy trials due to early progression in a relevant number of cases. The increase of the Lenalidomide dosage should result in an increased efficacy especially at the beginning and a higher cumulative dose of Lenalidomide.

The identification of patients intolerant to Lenalidomide by immunophenotyping of the T cells for validation is also part of this trial, because intolerance seems to be not dose dependent but may be caused by T cell activation. Therefore, early identification of patients intolerant to this form of modern immunochemotherapy and establishing efficient Lenalidomide based combination therapy is an important part of improvement of current CLL treatment.

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)

12

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

  • 奥地利
      • Salzburg、奥地利、5020
        • Universitätsklinik der PMU Salzburg, Univ-Klinik für Innere Medizin III
    • Tirol
      • Innsbruck、Tirol、奥地利、6020
        • Universitätsklinik für Innere Medizin Innsbruck, Klinische Abteilung für Hämatologie und Onkologie

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

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Signed written informed consent
  • Male or female ≥ 18 years of age
  • CLL (as determined by CD23+, CD5+, CD19+)
  • Treatment indication as defined by the NCI Workshop criteria (see appendix 6 and reference 10)
  • ECOG ≤ 2
  • No previous treatment of the CLL by chemotherapy, radiotherapy (except localized radiotherapy of 1 lymphatic area) or immunotherapy
  • Life expectancy > 6 months (except prognosis due to high risk CLL)

Exclusion Criteria:

  • Active bacterial, viral or fungal infection
  • Positivity for HIV, Hepatitis B or C
  • Patients with known history of thromboembolic events
  • Reduced organ functions and bone marrow dysfunction not due to CLL
  • Creatinine clearance of below 30 ml/min
  • Patients with known history of thromboembolic events
  • Patients with a history of other malignancies within 2 years prior to study entry (except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent)
  • Patients with medical co-morbid conditions that would require long term use (> 1 month) of systemic corticosteroids during study treatment
  • Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina
  • Other known co-morbidity with the potential to dominate survival
  • Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter's syndrome, or prolymphocytic leukemia (PLL))
  • Hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or any of the applied drugs
  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
  • Administration of any investigational agent(s) within 4 weeks prior to entry
  • Pregnancy or lactation
  • Medical or psychological condition which in the opinion of the Investigator would not permit the patient to complete the study or sign meaningful informed consent

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：Lenalidomide/Fludarabine/Rituximab

Lenalidomide: day 8-21 of cycle 1 and day 1-21 of cycles 2-6; Starting Dose: 5 mg (first 5 patients) and 10 mg (further 5 patients) increase Lenalidomide dose via dose levels (10)/15/20/25 mg/d every 28 days if no limiting toxicity occurs

Fludarabine: 25 mg/m2 iv d1-3 or 40 mg/m2 po d1-3; repeat every 28 days

Rituximab: 375 mg/m2 iv day 4 on cycle 1 and 500 mg/m2 iv day 1 on cycles 2-6; repeat every 28 days
药品：Lenalidomide

Lenalidomide: day 8-21 of cycle 1 and day 1-21 of cycles 2-6; Starting Dose: 5 mg (first 5 patients) and 10 mg (further 5 patients) increase Lenalidomide dose via dose levels (10)/15/20/25 mg/d every 28 days if no limiting toxicity occurs

Fludarabine: 25 mg/m2 iv d1-3 or 40 mg/m2 po d1-3; repeat every 28 days

Rituximab: 375 mg/m2 iv day 4 on cycle 1 and 500 mg/m2 iv day 1 on cycles 2-6; repeat every 28 days

其他名称：
  • 来那度胺

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
Tolerability of escalated starting dose
大体时间：12 month, 20 month
Interim analysis after completion of cylce 1 of the first 5 patients, final analysis after last pastient last visit Metrics: Number of patients experiencing defined dose limiting toxicities during cycle 1
12 month, 20 month

次要结果测量

结果测量
措施说明
大体时间
Establishment of maximal tolerated dose (MTD) of Lenalidomide in combination with FR
大体时间：20 month
20 month
Time to MTD
大体时间：20 month
20 month
Safety profile of the FRL combination
大体时间：20 month
Analysis of occuring adverse events during the study treatment according to Common Terminology Criteria for Adverse Events (CTCAE)
20 month
Response rates in all phases by 4-colour flow cytometric and ASO-PCR MRD analysis
大体时间：20 month
20 month
Risk factor analysis (FISH cytogenetics, CD38/ZAP-70 expression, mutation status)
大体时间：20 month
20 month
Longitudinal definition of T cell subsets (including prognostic EM T cells and Treg cells)+/- PD1
大体时间：20 month
20 month

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

Arbeitsgemeinschaft medikamentoese Tumortherapie

合作者

Celgene

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。

有用的网址

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

2012年6月1日

初级完成 (实际的)

2015年3月1日

研究完成 (实际的)

2015年10月1日

研究注册日期

首次提交

2012年10月4日

首先提交符合 QC 标准的

2012年10月8日

首次发布 (估计)

2012年10月10日

研究记录更新

最后更新发布 (估计)

2016年5月26日

上次提交的符合 QC 标准的更新

2016年5月25日

最后验证

2016年5月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • AGMT_CLL-9
  • 2011-004912-43 (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.

订阅