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

August 19, 2025 updated by: Cellectis S.A.

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Nantes, France, 44093
        • Recruiting
        • Centre Hospitalier Universitaire de Nantes (CHU de Nantes)-Hotel-Dieu
        • Principal Investigator:
          • Thomas Gastinne
        • Contact:
    • Auvergne Rhone Alpe
      • Pierre-Bénite, Auvergne Rhone Alpe, France, 69310
        • Recruiting
        • Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
        • Principal Investigator:
          • Emmanuel Bachy
        • Contact:
    • Ile De France
      • Paris, Ile De France, France, 75010
        • Recruiting
        • Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis - Centre Integre en Cancerologie
        • Principal Investigator:
          • Catherine Thieblemont
        • Contact:
    • Occitanie
      • Montpellier, Occitanie, France, 34295
        • Recruiting
        • Centre Hospitalier Universitaire de Montpellier (CHU Montpellier) - Hopital Saint-Eloi
        • Principal Investigator:
          • Guillaume Cartron
        • Contact:
  • Spain
      • Sevilla, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio (HUVR) - Instituto de Biomedicina de Sevilla (IBIS)
        • Principal Investigator:
          • Jose Antonio Perez Simon
        • Contact:
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
        • Principal Investigator:
          • Ana Alfonso
        • Contact:
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Medical Center (UCMC)
        • Principal Investigator:
          • Peter Riedell
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Harvard Medical School - Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Jeremy Abramson
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey (CINJ) - New Brunswick
        • Principal Investigator:
          • Matthew Matasar
        • Contact:
    • Texas
      • Austin, Texas, United States, 78704
        • Recruiting
        • Sarah Cannon - St. David South Austin Medical Center
        • Principal Investigator:
          • Aravind Ramakrishnan
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Incidence, nature and severity of adverse events and serious adverse events in relation to UCART20x22 and/or lymphodepletion
From study entry through month 12
Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs)
Time Frame: Up to Day 28 post UCART20x22 infusion
Up to Day 28 post UCART20x22 infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
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
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
From initiation of any study treatment to death from any cause, assessed up to Year 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cellectis S.A.

Investigators

  • Principal Investigator: Jeremy Abramson, MD, Harvard Medical School - Massachusetts General

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

October 25, 2022

First Submitted That Met QC Criteria

October 31, 2022

First Posted (Actual)

November 7, 2022

Study Record Updates

Last Update Posted (Actual)

August 24, 2025

Last Update Submitted That Met QC Criteria

August 19, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCART20x22_01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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