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Study to Evaluate the Feasibility and Safety of Autologous Cytokine-Induced Killer Cells (CIK_D332) in Combination With Tafasitamab and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (FOCUS)

2026年10月30日 更新者：Istituto Oncologico Veneto IRCCS

A Multicenter, Phase I Study to Evaluate the Feasibility and Safety of Autologous Cytokine-Induced Killer Cells (CIK_D332) in Combination With Tafasitamab and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): The FOCUS Study

This is a multicentre, Phase I trial of Cytokine Induced Killer-cells (CIK_D332) in combination with Tafasitamab and Lenalidomide in patients with Diffuse Large B-cell Lymphoma (DLBCL) who have relapsed or are refractory after at least one prior line of therapy including an anti-CD20 drug and are not candidates for high-dose chemotherapy with hematopoietic stem cell auto transplantation or CAR-T therapy. The plasticity of CIK cells allows a simple and immediate modulation of the combined therapeutic strategy through the replacement of the antibody used, without having to resort to genetic modification of the effector cells. Furthermore, thanks to the simultaneous expression of CD3 and CD16 receptors, the choice of the antibody to be used in the combination can fall on both monoclonal antibodies (bound by CD16) and bispecific antibodies (capable of binding and stimulating CD3), significantly expanding the spectrum of therapeutic options and the possibilities of combining these effector cells in anticancer therapy. To demonstrate this potential, expanded CIK cells from healthy donors were combined with obinutuzumab (anti-CD20 mAb), tafasitamab (anti-CD19 mAb), and blinatumomab (anti-CD19 bsAb) in parallel and tested against a large panel of hematologic malignancies. The combination with each of the three antibodies led to a significant increase in the intrinsic cytotoxic activity of CIKs, inducing ADCC activity against all the lines analysed. The resulting activity was comparable to, and in some cases even superior to, cytotoxicity induced by CD19-specific CAR-T cells. CIKs are able to recognize tumour cells in a MHC-independent manner through receptors typical of NK cells, in particular NKG2D, and to induce cell death by means of perforins and granzymes. In addition, thanks to the expression of the CD16 receptor, it is possible to stimulate their antibody-dependent cell-mediated cytotoxicity (ADCC) activity, increasing their intrinsic antitumor activity [10]. The end result of this approach is a lytic activity that combines the intrinsic MHC-independent cytotoxicity of CIKs with antibody-induced ADCC, resulting in enhanced antitumor efficacy. The project aims to provide a "proof of concept" in the clinic of a complementary or alternative therapeutic strategy to other anti-tumour immunotherapies, treating patients with relapsed or refractory DLBCL with chemotherapy-free immunotherapy.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

A total of 14 patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) will be enrolled. This sample size is intended to provide a sufficient cohort to evaluate the feasibility, safety, and preliminary efficacy of the combined therapy of CIK_D332, Tafasitamab, and Lenalidomide, while allowing for early assessment of the therapeutic approach in the specified patient population.

The treatment regimen consists of a combination of Tafasitamab, Lenalidomide, and CIK_D332, administered as follows:

  • Tafasitamab: Administered at a dose of 12 mg/kg IV.

    • Cycle 1 (28-day): Days 1, 4, 8, 15, and 22.
    • Cycles 2-3: Days 1, 8, 15, and 22.
    • Cycles 4-5: Days 1 and 15.

  • Lenalidomide: Administered at 25 mg orally on days 1-21 of each cycle (up to 5 cycles). Dose adjustments are applied according to the label for renal clearance and toxicity.

  • CIK_D332 Cells: Administered in cycles 2-5 (up to 8 doses total).

    • Administration: Infused after Tafasitamab on days 1 and 15. In patient with previous infusion-related reactions requiring premedication with glucocorticosteroids also in cycles 2-5, CIK_D332 will be infused the following day
    • Dosage: 3-5 x 106 cells/kg (total 225-300 x 106 cells).
    • Note: The number of doses (2-8) depends on CIK_D332 cell amount produced. Patients receiving fewer than 2 doses will not be evaluable for secondary objectives.

  • Maintenance: Following a clinical response, patients may continue treatment with Tafasitamab and Lenalidomide, without CIK_D332, until disease progression as per the label.

研究类型

介入性

注册 (估计的)

14

阶段

  • 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

  • 意大利
      • Verona、意大利
    • Pd
      • Padova、Pd、意大利、35128
        • Istituto Oncologico Veneto

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 至 99年 (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:

  • Signing of informed consent;

  • Patients of both sexes, aged ≥18 years;

  • Patients with relapsed/refractory DLBCL (including transformed indolent lymphoma with subsequent DLBCL recurrence) after at least one prior chemo-immonotherapy including anti-CD20 drug;

  • Patients with documented CD19 expression (by immunohistochemistry [IHC] or flow cytometry [FCM]) in lymphoma cells;

  • Patients not candidates for high-dose chemotherapy with hematopoietic stem cell auto transplantation or CAR-T therapy;.

  • Washout period following treatment with cytotoxic T-cell drugs before peripheral blood collection for CIK_D332 cell manufacturing:

    • minimum 2 weeks from systemic chemotherapy and targeted agents
    • minimum 12 weeks from lymphotoxic therapy (Bendamustine, Fludarabine, Cladribine, Pentostatin, loncastuximab, CAR-T)
    • minimum 7 days stop from corticosteroids
    • 2-4 weeks stop from immunosuppressants (e.g., for GVHD).

Exclusion Criteria:

  • ● Patients with known active malignancy;

    • Patients with a positive test for human immunodeficiency virus (HIV) or active hepatitis B or C;
    • Patients with active autoimmune disease requiring systemic treatment
    • Woman who is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study;
    • Patients suffering from Burkitt's lymphoma, aggressive lymphoma with rearrangement of MYC, BCL2 or BCL6;
    • Patients with > 4 lines of therapy for lymphoma;
    • Patients with known hypersensitivity to study antibodies, Human Serum Albumin (HSA), Dimethyl Sulfoxide (DMSO) or any formulation excipients of CIK_D332;
    • Patients with medical or psychological conditions that prevent participation;
    • Active, uncontrolled systemic bacterial, viral, fungal, or parasitic infections;.
    • Severe baseline organ failure (NYHA Class III/IV cardiac dysfunction, hepatic impairment with total bilirubin > 2.0× ULN, or renal failure with CrCl < 30 mL/min);.
    • Administration of live attenuated vaccines within 6 months prior to or following CIK_D332 cell infusion.

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：其他
  • 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：Experimental

Cytokine Induced Killer-cells (CIK_D332) in combination with Tafasitamab and Lenalidomide
药品：The treatment regimen consists of a combination of Tafasitamab, Lenalidomide, and CIK_D332

The treatment regimen consists of a combination of Tafasitamab, Lenalidomide, and CIK_D332, administered as follows:

  • Tafasitamab: Administered at a dose of 12 mg/kg IV.

    • Cycle 1 (28-day): Days 1, 4, 8, 15, and 22.
    • Cycles 2-3: Days 1, 8, 15, and 22.
    • Cycles 4-5: Days 1 and 15.

  • Lenalidomide: Administered at 25 mg orally on days 1-21 of each cycle (up to 5 cycles). Dose adjustments are applied according to the label for renal clearance and toxicity.

  • CIK_D332 Cells: Administered in cycles 2-5 (up to 8 doses total).

    • Administration: Infused after Tafasitamab on days 1 and 15. In patient with previous infusion-related reactions requiring premedication with glucocorticosteroids also in cycles 2-5, CIK_D332 will be infused the following day
    • Dosage: 3-5 x 106 cells/kg (total 225-300 x 106 cells).
    • Note: The number of doses (2-8) depends on CIK_D332 cell amount produced. Patients receiving fewer than 2 doses will not be evaluable for secondary objectives.

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
Feasibility of CIK (CIK_D332) cell therapy added to tafasitamab/lenalidomide in patients with relapsed/refractory DLBCL after at least one line of immuno-chemotherapy.
大体时间：Through study completion, an average of 3 years

The ability to expand CIK cells for therapy from peripheral blood of individual patient will be evaluated as CIK_D332 cell expansion rate > 6 x 108 cells at first production
Through study completion, an average of 3 years
Safety of CIK (CIK_D332) cell therapy added to tafasitamab/lenalidomide in patients with relapsed/refractory DLBCL after at least one line of immuno-chemotherapy.
大体时间：Through study completion, an average of 3 years

The safety of CIK_D332 cell therapy added to tafasitamab/lenalidomide will be evaluated as rate of CRS (total and grade III-IV), ICANS (total and grade III-IV) and rate and severity of treatment-emergent adverse events (TEAE).
Through study completion, an average of 3 years

次要结果测量

结果测量
措施说明
大体时间
Feasibility of performing therapy on an outpatient basis
大体时间：Through study completion, an average of 3 years

Rate of outpatient infusions/total infusion starting from the second CIK_D332 dose
Through study completion, an average of 3 years
Overall Response Rate (ORR) according to 2007 International Working Group response criteria for malignant lymphoma at the End of Treatment
大体时间：Through study completion, an average of 3 years

Overall Response Rate (ORR) will be defined as the proportion of patients who achieve a confirmed Complete Response (CR) or Partial Response (PR) after the end of treatment or death from any cause, whichever occurs first
Through study completion, an average of 3 years
Complete Response Rate (CRR) according to 2007 International Working Group response criteria for malignant lymphoma at End of Treatment
大体时间：Through study completion, an average of 3 years

Complete Response Rate (CRR) will be defined as the percentage of patients who achieve a Complete Response (CR) at the end of treatment
Through study completion, an average of 3 years
Progression Free survival (PFS) according to 2007 International Working Group response criteria for malignant lymphoma at End of Treatment
大体时间：Through study completion, an average of 3 years

Progression Free Survival (PFS) will be defined as the time from the date of the first tafasitamab infusion (Day 0) to the date of the first documentation of Progressive Disease (PD), or death from any cause, whichever occurs first
Through study completion, an average of 3 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

Istituto Oncologico Veneto IRCCS

合作者

Azienda Ospedaliera Universitaria Integrata Verona
Azienda ULSS 8 Berica

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 (估计的)

2027年1月31日

初级完成 (估计的)

2029年6月30日

研究完成 (估计的)

2029年6月30日

研究注册日期

首次提交

2026年10月23日

首先提交符合 QC 标准的

2026年10月23日

首次发布 (实际的)

2026年10月30日

研究记录更新

最后更新发布 (实际的)

2026年11月3日

上次提交的符合 QC 标准的更新

2026年10月30日

最后验证

2026年10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

  • IOV-DLBCL-01-2026-FOCUS
  • 2026-525494-39-00 (克蒂斯)

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.

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