Denna sida har översatts automatiskt och översättningens korrekthet kan inte garanteras. Vänligen se engelsk version för en källtext.

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)

30 oktober 2026 uppdaterad av: 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.

Studieöversikt

Status

Har inte rekryterat ännu

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

14

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

  • Italien
      • Verona, Italien
    • Pd
      • Padova, Pd, Italien, 35128
        • Istituto Oncologico Veneto

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 99 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Övrig
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Experimental

Cytokine Induced Killer-cells (CIK_D332) in combination with Tafasitamab and Lenalidomide
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
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.
Tidsram: 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.
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Feasibility of performing therapy on an outpatient basis
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Istituto Oncologico Veneto IRCCS

Samarbetspartners

Azienda Ospedaliera Universitaria Integrata Verona
Azienda ULSS 8 Berica

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Beräknad)

31 januari 2027

Primärt slutförande (Beräknad)

30 juni 2029

Avslutad studie (Beräknad)

30 juni 2029

Studieregistreringsdatum

Först inskickad

23 oktober 2026

Först inskickad som uppfyllde QC-kriterierna

23 oktober 2026

Första postat (Faktisk)

30 oktober 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

3 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

30 oktober 2026

Senast verifierad

1 oktober 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

OBESLUTSAM

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Prenumerera