NatHaLi-01: Study Evaluating UCART20x22 in B-Cell Non-Hodgkin Lymphoma

Sponsor

Cellectis S.A. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05607420

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
B-cell Non-Hodgkin Lymphoma (B-NHL)	Biological: UCART20x22 Biological: CLLS52	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2027

Anticipated Study Completion Date :

Nov 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
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	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 Other Names: Alemtuzumab

Arm

Intervention/Treatment

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

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

Other Names:

Alemtuzumab

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

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
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)
Active acute or chronic graft versus host disease
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)