Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma
Purpose
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).
Condition
- B-cell Non-Hodgkin Lymphoma (B-NHL)
Eligibility
- Eligible Ages
- Between 18 Years and 80 Years
- Eligible Genders
- All
- Accepts 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 - 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)
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dose finding part |
UCART20x22 tested at several dose levels until the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) is identified. Dose expansion part: UCART20x22 administered at the RP2D determined during the dose finding part |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Cellectis S.A.