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)
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.
調査の概要
状態
詳細な説明
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:
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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.
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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.
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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.
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Maintenance: Following a clinical response, patients may continue treatment with Tafasitamab and Lenalidomide, without CIK_D332, until disease progression as per the label.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Alessandra Sperotto, MD
- 電話番号：+39 0423 732336
- メール：alessandra.sperotto@iov.veneto.it
研究連絡先のバックアップ
- 名前：Gian Luca De Salvo, MD
- メール：clinical.trial@iov.veneto.it
研究場所
-
-
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Verona、イタリア
- Azienda Ospedaliera Universitaria integrata Verona
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コンタクト：
- Mauro Krampera, MD
- メール：mauro.krampera@univr.it
-
-
Pd
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Padova、Pd、イタリア、35128
- Istituto Oncologico Veneto
-
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
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Signing of informed consent;
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Patients of both sexes, aged ≥18 years;
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Patients with relapsed/refractory DLBCL (including transformed indolent lymphoma with subsequent DLBCL recurrence) after at least one prior chemo-immonotherapy including anti-CD20 drug;
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Patients with documented CD19 expression (by immunohistochemistry [IHC] or flow cytometry [FCM]) in lymphoma cells;
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Patients not candidates for high-dose chemotherapy with hematopoietic stem cell auto transplantation or CAR-T therapy;.
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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:
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● 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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：他の
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Experimental
Cytokine Induced Killer-cells (CIK_D332) in combination with Tafasitamab and Lenalidomide |
The treatment regimen consists of a combination of Tafasitamab, Lenalidomide, and CIK_D332, administered as follows:
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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.
時間枠：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.
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Feasibility of performing therapy on an outpatient basis
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IOV-DLBCL-01-2026-FOCUS
- 2026-525494-39-00 (Ctis)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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