A Phase 1/2a Study of UCART20x22 in B-Cell Non-Hodgkin Lymphoma [NatHaLi-01]

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cellectis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Jan 2026 → ongoing

Decision date (initial)

2023-03-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2022-501607-27-00

ClinicalTrials.gov

NCT05607420

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

For the Dose-Finding Part:
To assess the safety and tolerability and determine the MTD and/or RP2D of UCART20x22 in subjects with R/R mature B-NHL

For the Dose-Expansion Part:
To assess the safety and tolerability of UCART20x22 and confirm the RP2D in subjects with R/R LBCL

Secondary objectives 3

1. For the Dose-Finding Part: To assess the antitumor activity of UCART20x22 in subjects with R/R mature B-NHL
2. For the Dose-Finding Part: To identify the optimal lymphodepletion (LD) regimen to evaluate in dose-expansion part cohort(s)
3. For the Dose-Expansion Part: To assess the antitumor activity of UCART20x22 in subjects with specific subtypes of R/R large B-cell lymphoma (LBCL)

Conditions and MedDRA coding

Relapsed or refractory B-cell Non-Hodgkin lymphoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age 18 to 80 years
2. - Negative test result for hepatitis c virus (HCV) and human immunodeficiency virus (HIV).
3. - Women of childbearing potential (WOCBP) must have a negative, highly sensitive serum pregnancy test performed within 7 days prior to enrollment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22
6. - 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: o DLBCL o High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements o Transformed FL or transformed marginal zone lymphoma (MZL) o Follicular lymphoma Grade 3B
7. - R/R disease after at least 2 lines of prior treatment, which must have included: o 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 o An alkylating agent in combination with an anti-CD20 MoAb for FL o An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton’s tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL) o 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.
8. - At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma
9. - Prior lymphoma treatment-related toxicities resolved to baseline or ≤ Grade 1 prior to start of LD regimen
10. - Adequate organ function (renal, liver, cardiac, pulmonary, bone marrow)
11. - Negative serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
12. 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 25

1. Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD
2. Known hypersensitivity to any of the test materials or related compounds including murine and bovine products
3. History of hypersensitivity to alemtuzumab
4. History of neutralizing anti-drug antibody against alemtuzumab
5. Any known uncontrolled cardiovascular disease within 3 months of enrollment
6. Subjects requiring immunosuppressive treatment
7. Major surgery within 28 days prior to start of LD
8. 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)
9. Positive SARS-CoV2 viral PCR test within 3 days prior to initiation of LD
10. 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
11. 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
12. Active acute or chronic GvHD. Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
13. Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD
14. Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen
15. Prior cell or gene therapy (approved or investigational) within 6 weeks of the start of LD
16. Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22
17. Autologous HSCT infusion within 6 weeks of the start of LD
18. Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen)
19. Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL
20. Presence of an active and clinically relevant CNS disorder
21. Daily treatment with >20 mg prednisone or equivalent
22. Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
23. History of recurrent significant viral infection
24. Inability for any reason to receive appropriate antimicrobial prophylaxis against Pneumocystis jiroveci, herpes, viruses, and invasive fungal infections
25. More than 4 lines of therapy R/R B-NHL, prior to start of the LD regimen

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For the dose-finding part: Incidence, nature and severity of AEs and SAEs Proportion of subjects in each dose-level cohort with DLT during the DLT Observation Period For the dose-expansion part: Incidence, nature, and severity of AEs and SAEs during the dose-expansion part Incidence, nature, and severity of AEs and SAEs associated with LD in dose-expansion part

Secondary endpoints 1

1. : For the dose-finding and dose-expansion parts: Investigator assessed ORR according to Lugano response criteria. PFS, OS, and DoR Incidence, nature, and severity of AEs and SAEs associated with LD, associated antitumor activity, and corresponding host T-cell recovery and CAR T-cell expansion Quantitation of alemtuzumab levels in serum, evaluation of alemtuzumab PK parameters, TBNK panel and lymphocyte count

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cellectis

Sponsor organisation

Cellectis

Address

8 Rue De La Croix Jarry

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Cellectis

Contact name

clinical trial information desk

Public contact point

Organisation

Cellectis

Contact name

clinical trial information desk

Third parties 8

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications