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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04531046
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : August 12, 2022
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
B-Cell Lymphoma Refractory B-cell Lymphoma Recurrent Drug: axicabtagene ciloleucel Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: open-label, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 10, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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 Name: axi-cel

Primary Outcome Measures :
  1. Complete Metabolic Response (CMR) - determined by investigator [ Time Frame: 3 months from axi-cel infusion ]
    CMR from axi-cel infusion (without additional anticancer therapy) based on investigator disease assessment according to PET-scan (using the Lugano Response Criteria)

Secondary Outcome Measures :
  1. Complete Metabolic Response (CMR) - determined by central imaging review [ Time Frame: 3 months from axi-cel infusion ]
    CMR from axi-cel infusion (without additional anticancer therapy) determined by central imaging review (using the Lugano Response Criteria)

  2. Best objective response [ Time Frame: between Day 14 and Month 12 ]
    Percentage of CMR and Partial MR determined by investigator disease assessment

  3. Number of Serious Adverse Events (SAE) [ Time Frame: at 30 days after axi-cel infusion ]
  4. Event-free survival (EFS) based on investigator disease assessment [ Time Frame: at 3 months ]
  5. Event-free survival (EFS) based on investigator disease assessment [ Time Frame: at 6 months ]
  6. Event-free survival (EFS) based on investigator disease assessment [ Time Frame: at 12 months ]
  7. Event-free survival (EFS) based on central imaging review [ Time Frame: at 3 months ]
  8. Event-free survival (EFS) based on central imaging review [ Time Frame: at 6 months ]
  9. Event-free survival (EFS) based on central imaging review [ Time Frame: at 12 months ]
  10. Modified EFS (mEFS) based on investigator assessment [ Time Frame: at 6 months ]
  11. Modified EFS (mEFS) based on investigator assessment [ Time Frame: at 12 months ]
  12. Modified EFS (mEFS) based on central imaging review [ Time Frame: at 6 months ]
  13. Modified EFS (mEFS) based on central imaging review [ Time Frame: at 12 months ]
  14. Best objective response [ Time Frame: at 2 years ]
  15. Best objective response [ Time Frame: at 3 years ]
  16. Duration of response (DOR) [ Time Frame: at 2 years ]
  17. Duration of response (DOR) [ Time Frame: at 3 years ]
  18. Overall survival (OS) from leukaphaeresis and Axi-cel infusion [ Time Frame: at 2 years ]
  19. Overall survival (OS) from leukaphaeresis and Axi-cel infusion [ Time Frame: at 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04531046

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Contact: Véronique Vacher +33 (0)4 27 01 27 14

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CH Liège Recruiting
Liège, Belgium, 4000
Contact: Christophe Bonnet, MD         
Principal Investigator: Christophe BONNET, MD         
CHU de Bordeaux - Hôpital Haut Lévêque Recruiting
Bordeaux, France
Contact: François-Xavier GROS         
Principal Investigator: François-Xavier GROS         
CHU Clermont Ferrand - Hôpital Estaing Recruiting
Clermont-Ferrand, France
Contact: Olivier BAY         
Principal Investigator: Olivier BAY         
APHP - Hôpital Henri Mondor Recruiting
Créteil, France
Contact: François LEMONNIER         
CHU de Dijon - Hôpital le Bocage Recruiting
Dijon, France, 21000
Contact: Olivier CASASNOVAS, MD         
Hôpital Claude Huriez Recruiting
Lille, France, 59037
Contact: Franck MORSCHHAUSER, MD   
Principal Investigator: Franck MORSCHHAUSER, MD         
Hôpital Saint Eloi Recruiting
Montpellier, France, 34295
Contact: Guillaume CARTRON, MD         
Principal Investigator: Guillaume CARTRON, MD         
CHU de Nantes - Hôtel Dieu Recruiting
Nantes, France, 44093
Contact: Steven LE GOUILL, Pr         
APHP - Hôpital Saint Louis Recruiting
Paris Cedex 10, France, 75475
Contact: Catherine Thieblemont, MD         
Hopital La Pitié Salpétriere Recruiting
Paris, France
Contact: Sylvain Choquet    +33 (0)1 42 16 28 26   
Hôpital Saint Antoine Recruiting
Paris, France
Contact: Rémy DULERY         
Principal Investigator: Rémy DULERY         
Centre Hospitalier Lyon Sud Recruiting
Pierre Bénite, France, 69495
Contact: Emmanuel BACHY, MD         
CHU de Rennes - Hôpital de Pontchaillou Recruiting
Rennes, France, 35003
Contact: Roch HOUOT, MD         
IUCT Oncopole Recruiting
Toulouse, France
Contact: Lucie OBERIC         
Principal Investigator: Lucie OBERIC         
CHU Brabois Recruiting
Vandoeuvre les Nancy, France, 54511
Contact: Pierre FEUGIER, MD         
Principal Investigator: Pierre FEUGIER, MD         
Institut de Cancérologie Gustave Roussy Recruiting
Villejuif, France
Contact: Cristina CASTILLA LLORENTE         
Principal Investigator: Cristina CASTILLA LLORENTE         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
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Principal Investigator: Roch Houot, PhD Rennes University Hospital, Rennes, France
Principal Investigator: François Lemonnier, PhD Henri Mondor Hospital, Créteil, France
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Responsible Party: The Lymphoma Academic Research Organisation Identifier: NCT04531046    
Other Study ID Numbers: ALYCANTE
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: August 12, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin