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NCT07906080

PHASE1

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

Sponsor: Istituto Oncologico Veneto IRCCS

View on ClinicalTrials.gov

Summary

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - 99 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2027-01-31

Completion Date

2029-06-30

Last Updated

2026-11-03

Healthy Volunteers

Conditions

Diffuse Large B-Cell Lymphoma (DLBCL)

Interventions

DRUG

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.

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.

Locations (2)

Istituto Oncologico Veneto

Padova, Pd, Italy

Azienda Ospedaliera Universitaria integrata Verona

Verona, Italy