Clinical trial NCT05607420: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL)
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®)
Lead sponsor: Cellectis S.A.
Sponsor class: INDUSTRY
First posted: 2022-11-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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
* 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)

Primary outcomes:
measure: Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability]
timeFrame: From study entry through month 12
measure: Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 28 post UCART20x22 infusion
Secondary outcomes:
measure: Investigator assessed overall response rate (ORR) according to Lugano Response Criteria for Malignant Lymphoma
timeFrame: At Day 28, Day 84, Month 6, Month 9, Month 12
measure: Duration of Response
timeFrame: From achievement of the initial response to disease relapse/progression or death from any cause, assessed up to Month 12
measure: Progression-free survival (PFS)
timeFrame: 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
measure: Overall survival
timeFrame: From initiation of any study treatment to death from any cause, assessed up to Year 15
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Austin
country: United States
facility: Sarah Cannon - St. David South Austin Medical Center
state: Texas
city: Pierre-Bénite
country: France
facility: Hôpital Lyon Sud
state: Auvergne Rhone Alpe
city: Paris
country: France
facility: Hôpital Saint Louis
state: Ile de France
city: Alexis-Ricordeau
country: France
facility: CHU de Nantes
state: Nantes
city: Montpellier
country: France
facility: CHU de Montpellier
state: Occitanie
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: Massachusetts General Hospital
name: Jeremy Abramson, MD
role: PRINCIPAL_INVESTIGATOR
References: