Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma

Official title

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)

Overview

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

• Biological UCART20x22
  Allogeneic engineered T-cells expressing anti-CD20 and anti-CD22 Chimeric Antigen Receptors given following a lymphodepletion regimen
• Biological CLLS52
  A monoclonal antibody that recognizes a CD52 antigen

Primary outcome measures

• Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability] [Time frame: From study entry through month 12]
• Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs) [Time frame: Up to Day 28 post UCART20x22 infusion]

Secondary outcome measures (4)

• Investigator assessed overall response rate (ORR) according to Lugano Response Criteria for Malignant Lymphoma [Time frame: At Day 28, Day 84, Month 6, Month 9, Month 12]
• Duration of Response [Time frame: From achievement of the initial response to disease relapse/progression or death from any cause, assessed up to Month 12]
• Progression-free survival (PFS) [Time frame: 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 [Time frame: From initiation of any study treatment to death from any cause, assessed up to Year 15]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• The University of Chicago Medical Center (UCMC) — Chicago
• Harvard Medical School - Massachusetts General Hospital — Boston
• Rutgers Cancer Institute of New Jersey (CINJ) - New Brunswick — New Brunswick
• Sarah Cannon - St. David South Austin Medical Center — Austin

France · 4 centers

• Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud — Pierre-Bénite
• Centre Hospitalier Universitaire de Montpellier (CHU Montpellier) - Hopital Saint-Eloi — Montpellier
• Centre Hospitalier Universitaire de Nantes (CHU de Nantes)-Hotel-Dieu — Nantes
• Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis - Centre Integre en Ca — Paris

Spain · 2 centers

• Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona — Pamplona
• Hospital Universitario Virgen del Rocio (HUVR) - Instituto de Biomedicina de Sevilla (IBIS — Seville

Identifiers

NCT: NCT05607420 · UCART20x22_01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗