A Phase 1/2a Study of UCART20x22 in B-Cell Non-Hodgkin Lymphoma [NatHaLi-01]

Trial details

Who runs it

Cellectis

Trial code

NCT05607420EU 2022-501607-27-00

Record updated

21 October 2026

Original description

For the Dose-Finding Part: To assess the safety and tolerability and determine the MTD and/or RP2D of UCART20x22 in subjects with R/R mature B-NHLRead full original descriptionShow less

Open-label dose-finding and dose-expansion study to evaluate the safety, expansion, persistence, and clinical activity of UCART20x22 in subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma (B-NHL)

For the Dose-Finding Part: To assess the safety and tolerability and determine the MTD and/or RP2D of UCART20x22 in subjects with R/R mature B-NHL

For the Dose-Expansion Part: To assess the safety and tolerability of UCART20x22 and confirm the RP2D in subjects with R/R LBCL

Inclusion: Age 18 to 80 years; Adequate organ function (renal, liver, cardiac, pulmonary, bone marrow); Negative serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection; Autologous hematopoietic stem cells must be available prior to the start of the LD regimen if the subject is considered high-risk for prolonged hematologic toxicity; Negative test result for hepatitis c virus (HCV) and human immunodeficiency virus (HIV); Women of childbearing potential (WOCBP) must have a negative, highly sensitive serum pregnancy test performed within 7 days prior to enrollment; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22; Subjects with NHL subtypes defined by WHO •Dose-finding part: R/R mature B-NHL (except chronic lymphocytic leukemia/small lymphocytic leukemia [CLL/SLL], Richter’s transformation from prior CLL/SLL, Burkitt’s lymphoma, and Waldenstrom’s macroglobulinemia) •Dose-expansion Part: R/R LBCL defined as: o DLBCL o High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements o Transformed FL or transformed marginal zone lymphoma (MZL) o Follicular lymphoma Grade 3B; R/R disease after at least 2 lines of prior treatment, which must have included: o An Anti-CD20 MoAb and an anthracycline for DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma (PMBCL), or transformed FL or MZL o An alkylating agent in combination with an anti-CD20 MoAb for FL o An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton’s tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL) o Autologous anti-CD19 CAR T-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-CD19 CAR T-cell therapy; At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma; Prior lymphoma treatment-related toxicities resolved to baseline or ≤ Grade 1 prior to start of LD regimen.

Exclusion: Prior use of an investigational product (except for cell or gene therapies and MoAbs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of LD regimen; Previous approved therapy including chemotherapy, biologic (except MoAbs), or targeted therapy for R/R B-NHL with 5 half-lives or within 14 days, whichever is shorter, prior to start of the LD regimen; Active acute or chronic GvHD. Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD; Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD; Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen; Prior cell or gene therapy (approved or investigational) within 6 weeks of the start of LD; Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22; Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen); Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL; Daily treatment with >20 mg prednisone or equivalent; More than 4 lines of therapy R/R B-NHL, prior to start of the LD regimen; Major surgery within 28 days prior to start of LD; Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix); Positive SARS-CoV2 viral PCR test within 3 days prior to initiation of LD; Known hypersensitivity to any of the test materials or related compounds including murine and bovine products; Presence of an active and clinically relevant CNS disorder; Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens; History of recurrent significant viral infection; Inability for any reason to receive appropriate antimicrobial prophylaxis against Pneumocystis jiroveci, herpes, viruses, and invasive fungal infections; History of hypersensitivity to alemtuzumab; History of neutralizing anti-drug antibody against alemtuzumab; Any known uncontrolled cardiovascular disease within 3 months of enrollment; Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD; Autologous HSCT infusion within 6 weeks of the start of LD; Subjects requiring immunosuppressive treatment.

ClinicalTrials.gov NCT05607420 · EU CTIS 2022-501607-27-00