B-cell Non-Hodgkin Lymphoma (B-NHL)
Conditions
Keywords
B-cell Non-Hodgkin Lymphoma (B-NHL), Relapsed/Refractory B-NHL, Universal Chimeric Antigen Receptor T-Cell (UCAR-T) Therapy, Allogeneic, Transcription Activator-Like Effector Nuclease (TALEN®)
Brief summary
First-in-human, open-label, dose-finding and dose-expansion study of UCART20x22 administered intravenously in subjects with relapsed or refractory B-Cell Non-Hodgkin Lymphoma (B-NHL). The purpose of this study is to evaluate the safety and clinical activity of UCART20x22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).
Interventions
BIOLOGICALUCART20x22
Allogeneic engineered T-cells expressing anti-CD20 and anti-CD22 Chimeric Antigen Receptors given following a lymphodepletion regimen
BIOLOGICALCLLS52
A monoclonal antibody that recognizes a CD52 antigen
Sponsors
Cellectis S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Exclusion criteria
* 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 * \> 4 lines of therapy R/R B-NHL 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 months 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability] | From study entry through month 12 | Incidence, nature and severity of adverse events and serious adverse events in relation to UCART20x22 and/or lymphodepletion |
| Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs) | Up to Day 28 post UCART20x22 infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Investigator assessed overall response rate (ORR) according to Lugano Response Criteria for Malignant Lymphoma | At Day 28, Day 84, Month 6, Month 9, Month 12 |
| Duration of Response | From achievement of the initial response to disease relapse/progression or death from any cause, assessed up to Month 12 |
| Progression-free survival (PFS) | From the first day of any study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 12 |
| Overall survival | From initiation of any study treatment to death from any cause, assessed up to Year 15 |
Countries
France, Spain, United States
Contacts
Primary ContactCellectis Central Contact
Outcome results
None listed