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。

Venetoclax 治疗（26 个周期）与 6 个周期或 12 个周期的 Epcoritamab 治疗复发或难治性 CLL 或 SLL 患者 (AETHER)

2026年9月30日 更新者：Stichting Hemato-Oncologie voor Volwassenen Nederland

在复发或难治性慢性淋巴细胞白血病或小淋巴细胞淋巴瘤患者中使用 6 个周期或 12 个周期的 Epcoritamab 治疗 Venetoclax（26 个周期）的前瞻性随机 I/II 期试验

In this study, efficacy and safety of 2 regimens that combine the CD3-CD20 T cell engager epcoritamab with venetoclax will be tested in relapsed/refractory CLL and SLL patients. The trial starts with phase I part to establish the recommended dose level (RDL) of epcoritamab in the combination with venetoclax for the phase II trial.

研究概览

地位

招聘中

条件

干预/治疗

研究类型

介入性

注册 (估计的)

112

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。

学习联系方式

研究联系人备份

学习地点

  • 丹麦
      • Aalborg、丹麦
        • 撤销
        • DK-Aalborg-ALBOGUH
      • Copenhagen、丹麦
        • 招聘中
        • DK-Copenhagen-RIGSHOSPITALET
      • Odense、丹麦
        • 招聘中
        • DK-Odense-OUH
  • 德国
      • Berlin、德国
        • 撤销
        • DE-Berlin-HELIOSBERLINBUCH
      • Cologne、德国
        • 招聘中
        • DE-Köln-UKKOELN
      • Freiburg im Breisgau、德国
        • 招聘中
        • DE-Freiburg-UNIKLINIKFREIBURG
      • Greifswald、德国
        • 撤销
        • DE-Greifswald-UNIGREIFSWALD
      • Halle、德国
        • 招聘中
        • DE-Halle-UMH
      • Kiel、德国
        • 招聘中
        • DE-Kiel-UKSH
      • Münster、德国
        • 招聘中
        • DE-Munster-GEMEINSCHAFTSPRAXIS
      • Stuttgart、德国
        • 招聘中
        • DE-Stuttgart-RBK
      • Ulm、德国
        • 招聘中
        • DE-Ulm-UNIKLINKULM
  • 比利时
      • Antwerp、比利时
        • 招聘中
        • BE-Antwerpen-ZNASTUIVENBERG
      • Roeselare、比利时
        • 招聘中
        • BE-Roeselare-AZDELTA
  • 澳大利亚
      • Melbourne、澳大利亚
        • 招聘中
        • AU-Melbourne-ALFRED
      • Melbourne、澳大利亚
        • 招聘中
        • AU-Melbourne-MONASH
      • Melbourne、澳大利亚
        • 招聘中
        • AU-Melbourne-SVHM
  • 荷兰
      • 's-Hertogenbosch、荷兰
        • 招聘中
        • NL-Den Bosch-JBZ
      • Alkmaar、荷兰
        • 撤销
        • NL-Alkmaar-NWZ
      • Amersfoort、荷兰
        • 招聘中
        • NL-Amersfoort-MEANDERMC
      • Amsterdam、荷兰
        • 招聘中
        • NL-Amsterdam-AMC
      • Dordrecht、荷兰
        • 招聘中
        • NL-Dordrecht-ASZ
      • Ede、荷兰
        • 招聘中
        • NL-Ede-ZGV
      • Eindhoven、荷兰
        • 招聘中
        • NL-Eindhoven-CATHARINA
      • Groningen、荷兰
        • 招聘中
        • NL-Groningen-UMCG
      • Leeuwarden、荷兰
        • 招聘中
        • NL-Leeuwarden-MCL
      • The Hague、荷兰
        • 招聘中
        • NL-Den Haag-HAGA
      • Tilburg、荷兰
        • 招聘中
        • NL-Tilburg-ETZ
      • Utrecht、荷兰
        • 招聘中
        • NL-Utrecht-UMCUTRECHT

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:

  • Documented relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment

  • Requiring treatment according to IWCLL criteria (appendix A);

  • Age at least 18 years;

  • ECOG/WHO performance status 0-2;

  • In case of prior venetoclax treatment, enrollment can only occur at least 24 months after end of treatment and patients must not have progressed during venetoclax treatment;

  • Adequate BM function defined as:

    • Hemoglobin >5.6 mmol/l or Hb > 9 g/dL, unless low Hb is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
    • Absolute neutrophil count (ANC) >1.0 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
    • Platelet count >30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL infiltration in the BM;

  • Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/min (Cockcroft-Gault appendix F);

  • Adequate liver function as indicated:

    • Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x upper limit of normal (ULN);
    • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or controlled autoimmune hemolytic anemia);

  • Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN; unless receiving anticoagulation;

  • Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded; Please note: For patients positive for anti-HBc, HBV-DNA PCR has to be repeated every month until 12 months after last dose of study treatment.

  • Patient is able and willing to adhere to the study visit schedule and other protocol requirements;

  • Patient is capable of giving informed consent;

  • Written informed consent.

Exclusion Criteria:

  • Active CLL/SLL directed therapy within the last 14 days;

  • Prior treatment with a CD3 × CD20 bispecific antibody or CAR T-cell therapy

  • Transformation of CLL (Richter's transformation);

  • Prior allogeneic stem cell transplantation and/or solid organ transplantation;

  • Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML);

  • Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment;

  • Known allergy to xanthine oxidase inhibitors and/or rasburicase;

  • History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components);

  • Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease);

  • Active fungal, bacterial, and/or viral infection CTCAEgrade > 1; Please note: active controlled as well as chronic/recurrent infections are at risk of reactivation/infection during treatment;

  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.);

  • Patient known to be HIV-positive;

  • Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor/inducer (see appendix J) or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists;

  • CTCAE grade III-IV cardiovascular disease including but not limited to:

    • Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association (see appendix E), uncontrolled clinically significant cardiac arrhythmia (CTCAE grade II or higher), or clinically significant electrocardiogram (ECG) abnormalities.
    • Myocardial infarction, intracranial bleed, or stroke within the past 6 months.
    • Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >480 msec. NOTE: this criterion does not apply to subjects with a left bundle branch block.
    • Stroke or intracranial hemorrhage within 6 months prior to registration.

  • Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);

  • Severe neurological or psychiatric disease (CTCAE grade III-IV, see appendix D);

  • Neuropathy > CTCAE grade II

  • Patient who has difficulty with or are unable to swallow oral medication, or have significant gastrointestinal disease that would limit absorption of oral medication;

  • Vaccination with live vaccines within 28 days prior to registration;

  • Use of any other experimental drug or therapy within 28 days of registration;

  • Major surgery within 28 days prior to registration;

  • Pregnant women and nursing mothers;

  • Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) during study treatment and for 12 months after last dose of epcoritamab and 30 days after last dose of venetoclax;

  • Previous participation in the HOVON 139 CLL or HOVON 140 CLL trial and eligible for and willing to participate in the HOVON 159 CLL trial;

  • Current participation in other clinical trial with medicinal products;

  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

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：随机化
  • 介入模型：并行分配
  • 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：Arm A

6 cycles epcoritamab + 26 cycles venetoclax
药品：Epcoritamab

Number of cycles of epcoritamab is either 6 (cycle 1-6) or 12 (cycle 1-12). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

药品：Venetoclax

All patients will receive venetoclax cycle 1-26 (a 5 week ramp-up of venetoclax will precede the first cycle). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.
实验性的：Arm B

12 cycles epcoritamab + 26 cycles venetoclax
药品：Epcoritamab

Number of cycles of epcoritamab is either 6 (cycle 1-6) or 12 (cycle 1-12). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

药品：Venetoclax

All patients will receive venetoclax cycle 1-26 (a 5 week ramp-up of venetoclax will precede the first cycle). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

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) for the combination of venetoclax and epcoritamab based on dose limiting toxicity (DLT)
大体时间：6-12 months

endpoint for phase I and both arms
6-12 months
• Undetectable minimal residual disease <10-4 (uMRD) in BM in absence of progression according to IWCLL criteria at 12 weeks after cycle 26
大体时间：29 months

endpoint for phase II and both arms
29 months

次要结果测量

结果测量
措施说明
大体时间
• Minimal residual disease (MRD) status in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24 and 12 weeks after cycle 26; following treatment: every 3 months for the first year, then every 6 months until relapse or until 6 years after registration
大体时间：6 years

both arms
6 years
• Progression free survival (PFS), defined as time from registration to the first occurrence of disease progression or death from any cause, whichever occurs first.
大体时间：6 years

both arms
6 years
Overall survival (OS), defined as the time from registration to death from any cause.
大体时间：6 years

both arms
6 years
Best overall response rate (ORR) defined as the proportion of patients with a complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) according to IWCLL 2018 criteria.
大体时间：6 years

both arms
6 years
• Event free survival (EFS), defined as time from randomization to date start of next CLL treatment, progression or death, whichever comes first.
大体时间：6 years

both arms
6 years
• Time to next CLL treatment (TTNT), defined as time from randomization to next new line of treatment.
大体时间：6 years

both arms
6 years
• Treatment free survival (TFS), defined as time from date of last protocol treatment to date start of next (new) line of treatment, or death from any cause, whichever comes first.
大体时间：6 years

both arms
6 years
Duration of response (DOR), defined as time from first response (i.e., ≥PR and CR) to PD or death from any cause.
大体时间：6 years

both arms
6 years
• Depth (level) of minimal residual disease (MRD) measured in BM after cycle 9 and 12 weeks after cycle 26.
大体时间：29 months

both arms
29 months
• Depth (level) of minimal residual disease measured in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24, 12 weeks after cycle 26 and thereafter every 3 months for the first year, then every 6 months until relapse or until 6 years after registration
大体时间：6 years

both arms
6 years
Safety parameters: Type, frequency, and severity of- adverse events (AEs) and- adverse events of special interest (AESI) and their relationship to study treatment (determined according to CTCAE v5.0).
大体时间：6 years

both arms
6 years
Health-related quality of life (QoL) by EORTC QLQ-C30 questionnaires.
大体时间：6 years

both arms
6 years
Health-related quality of life (QoL) by QLQ-CLL17 questionnaires.
大体时间：6 years

both arms
6 years
Health-related quality of life (QoL) by PRO-CTCAE questionnaires.
大体时间：6 years

both arms
6 years

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

Stichting Hemato-Oncologie voor Volwassenen Nederland

合作者

Nordic CLL Study Group (NCLLSG)
The Australasian Leukaemia & Lymphoma Group (ALLG)
German CLL Study Group (GCLLSG)

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 (实际的)

2024年4月15日

初级完成 (估计的)

2029年3月1日

研究完成 (估计的)

2032年12月1日

研究注册日期

首次提交

2023年2月1日

首先提交符合 QC 标准的

2023年3月28日

首次发布 (实际的)

2023年3月30日

研究记录更新

最后更新发布 (实际的)

2026年10月5日

上次提交的符合 QC 标准的更新

2026年9月30日

最后验证

2026年9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

  • HO165 CLL

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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