Axi-Cel as a 2nd Line Therapy in Patients With Relapsed/Refractory Aggressive B Lymphoma Ineligible to Autologous Stem Cell Transplantation

Phase 2, Open-Label Study Evaluating Axi-Cel as a 2nd Line Therapy in Patients With Relapsed/Refractory Aggressive B-Non Hodgkin Lymphoma (B-NHL) Who Are Ineligible to Autologous Stem Cell Transplantation

This is a phase 2, open-label, multicenter study evaluating axicabtagene ciloleucel (axi-cel) as a 2nd line therapy in patients with Relapsed/Refractory aggressive B-NHL who are ineligible to receive Autologous Stem Cell Transplantation but eligible to receive CAR T-cell therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Lymphoma Recurrent; B-Cell Lymphoma Refractory
• Intervention / Treatment: Drug: axicabtagene ciloleucel

Detailed Description

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy directed against CD19 which has been approved for the treatment of relapse/refractory diffuse large B-cell lymphoma DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after 2 or more lines of systemic therapy.

But administrating CAR T-cells earlier in the therapeutic strategy may be beneficial to patients.

Axi-cel will improve the outcome of patients with DLBCL who are refractory or relapse early (i.e. within 1 year from end of treatment) after first-line therapy and who are not eligible for Autologous Stem Cell Transplantation (ASCT).

Transplant-ineligible patients will include those who are deemed ineligible for high-dose chemotherapy and Hematopoietic Stem Cell Transplantation (HSCT) due to age, comorbidity, or prior ASCT.

The primary endpoint will be complete metabolic response (CMR) at 3 months after Axi-cel infusion.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • CH Liège
• France
  • Bordeaux, France
    • CHU de Bordeaux - Hôpital Haut Leveque
  • Clermont-Ferrand, France
    • CHU Clermont Ferrand - Hôpital Estaing
  • Créteil, France
    • APHP - Hopital Henri Mondor
  • Dijon, France, 21000
    • CHU de Dijon - Hôpital le Bocage
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Montpellier, France, 34295
    • Hopital Saint Eloi
  • Nantes, France, 44093
    • CHU de Nantes - Hotel Dieu
  • Paris, France
    • Hôpital Saint Antoine
  • Paris, France
    • Hôpital La Pitié Salpêtrière
  • Paris, France, 75475
    • APHP - Hôpital Saint Louis
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35003
    • CHU de Rennes - Hôpital de Pontchaillou
  • Toulouse, France
    • IUCT Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • Chu Brabois
  • Villejuif, France
    • Institut de Cancérologie Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient who understands and speaks one of the country official languages and signed Informed Consent Form
• Histologically proven relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL) of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), follicular lymphoma Grade 3B per World Health Organization (WHO) 2016 classification and Primary mediastinal Bcell lymphomas. Indolent B-NHL who transformed into aggressive B-NHL and were previously treated with Rituximab-Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP) are eligible.
• Tumoral tissue (at diagnosis or relapse) available for central pathology review, exploratory endpoints and ancillary studies
• Positron-emission tomography (PET)-positive disease
• Patients must have received adequate first-line therapy including at a minimum: an anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (CHOP) or CHOP-like chemotherapy
• Relapsed or refractory disease after first-line chemoimmunotherapy (full dose of R-CHOP or R-CHOP-like regimen), documented by PET-scan
• At least 2 weeks must have elapsed since any prior systemic cancer therapy at the time the patient provides consent
• Patients must be autologous stem cell transplantation (ASCT)-ineligible
• Patients must be CAR-T-eligible
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential)

Exclusion Criteria:

• Patients who received more than one prior line of systemic therapy
• Patients who are intolerant to first-line therapy or who received suboptimal first-line therapy, including dose-reduced R-CHOP ("R-miniCHOP"), and those who discontinued prematurely first-line therapy due to toxicity are not eligible
• Prior CD19 targeted therapy
• Patients with cardiac atrial or cardiac ventricular lymphoma involvement
• Requirement for urgent therapy due to tumor mass effects, such as bowel obstruction or blood vessel compression
• Patient with clinically significant pleural effusion
• History of another primary malignancy that has not been in remission for at least 2 years (except for nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast))
• Patients with detectable Central Nervous System (CNS) lymphoma
• History or presence of non-malignant CNS disorder, such as seizure disorder requiring anti-convulsive therapy, cerebellar disease, or any autoimmune disease with CNS involvement disease
• Active hepatitis B or hepatitis C infection, positive serology of human immunodeficiency virus (HIV) and syphilis at the time of screening
• Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or axi-cel administration
• History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History of autoimmune disease requiring systemic immunosuppression and/or systemic disease modifying agents within the last year
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening.
• History of severe immediate hypersensitivity reaction to tocilizumab or any of the agents used in this study
• History of severe immediate hypersensitivity reaction attributed to aminoglycosides, cyclophosphamide and fludarabine
• Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the course of the study
• Women of childbearing potential who are pregnant or breastfeeding (from the time of consent during treatment and for at least 6 months after conditioning chemotherapy dosing or axicabtagene ciloleucel dosing, whichever is later)
• In the investigator's judgment, the patient is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
• Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: axicabtagene ciloleucel; Single infusion administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg	Drug: axicabtagene ciloleucel; Patient-specific (autologous) product cryopreserved in cryostorage bag; Other Names: axi-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Metabolic Response (CMR) - determined by investigator	CMR from axi-cel infusion (without additional anticancer therapy) based on investigator disease assessment according to PET-scan (using the Lugano Response Criteria)	3 months from axi-cel infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Metabolic Response (CMR) - determined by central imaging review	CMR from axi-cel infusion (without additional anticancer therapy) determined by central imaging review (using the Lugano Response Criteria)	3 months from axi-cel infusion
Best objective response	Percentage of CMR and Partial MR determined by investigator disease assessment	between Day 14 and Month 12
Number of Serious Adverse Events (SAE)		at 30 days after axi-cel infusion
Event-free survival (EFS) based on investigator disease assessment		at 3 months
Event-free survival (EFS) based on investigator disease assessment		at 6 months
Event-free survival (EFS) based on investigator disease assessment		at 12 months
Event-free survival (EFS) based on central imaging review		at 3 months
Event-free survival (EFS) based on central imaging review		at 6 months
Event-free survival (EFS) based on central imaging review		at 12 months
Modified EFS (mEFS) based on investigator assessment		at 6 months
Modified EFS (mEFS) based on investigator assessment		at 12 months
Modified EFS (mEFS) based on central imaging review		at 6 months
Modified EFS (mEFS) based on central imaging review		at 12 months
Best objective response		at 2 years
Best objective response		at 3 years
Duration of response (DOR)		at 2 years
Duration of response (DOR)		at 3 years
Overall survival (OS) from leukaphaeresis and Axi-cel infusion		at 2 years
Overall survival (OS) from leukaphaeresis and Axi-cel infusion		at 3 years

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Investigators: Principal Investigator: Roch Houot, PhD, Rennes University Hospital, Rennes, France; Principal Investigator: François Lemonnier, PhD, Henri Mondor Hospital, Créteil, France

Publications and helpful links

General Publications

• Charton E, Anota A, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Dulery R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Llamas Gutierrez F, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, Lemonnier F, Houot R. Health-related quality of life after second-line axi-cel in transplant-ineligible patients with large B-cell lymphoma. Blood Adv. 2026 Mar 10;10(5):1773-1782. doi: 10.1182/bloodadvances.2025018057.
• Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Dulery R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, Lemonnier F. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial. Nat Med. 2023 Oct;29(10):2593-2601. doi: 10.1038/s41591-023-02572-5. Epub 2023 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): April 19, 2022
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; axicabtagene ciloleucel
• Other Study ID Numbers: ALYCANTE

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: No
• Studies a U.S. FDA-regulated device product: No