Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma

Eligibility Criteria

• * 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: i. DLBCL; ii. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; iii. Transformed FL or transformed marginal zone lymphoma (MZL); iv. Follicular lymphoma Grade 3B
• * R/R disease after at least 2 lines of prior treatment, which must have included:
• * -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
• * -An alkylating agent in combination with an anti-CD20 MoAb for FL
• * -An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton's tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL)
• * -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 (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, CD19 negative disease, etc.)
• * 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
• * 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
• * 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
• * Autologous HSCT infusion within 6 weeks of the start of LD
• * Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD
• * Active acute or chronic graft versus host disease (GvHD). Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
• * 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
• * Presence of an active and clinically relevant CNS disorder
• * Daily treatment with \>20 mg prednisone or equivalent
• * Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
• * History of hypersensitivity to alemtuzumab
• * History of neutralizing anti-drug antibody against alemtuzumab
• * Any known uncontrolled cardiovascular disease within 3 months of enrollment
• * Subjects requiring immunosuppressive treatment
• * 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)