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

B-Cell Lymphoma Refractory Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04531046
• Other study ID #: ALYCANTE
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 10, 2021
• Est. completion date: June 2024

Study information

• Verified date: September 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: June 2024
• Est. primary completion date: April 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Lymphoma Recurrent
• B-Cell Lymphoma Refractory
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• axicabtagene ciloleucel
Patient-specific (autologous) product cryopreserved in cryostorage bag

Locations

Country	Name	City	State
Belgium	CH Liège	Liège
France	CHU de Bordeaux - Hôpital Haut Lévêque	Bordeaux
France	CHU Clermont Ferrand - Hôpital Estaing	Clermont-Ferrand
France	APHP - Hôpital Henri Mondor	Créteil
France	CHU de Dijon - Hôpital le Bocage	Dijon
France	Hôpital Claude Huriez	Lille
France	Hôpital Saint Eloi	Montpellier
France	CHU de Nantes - Hôtel Dieu	Nantes
France	Hopital La Pitié Salpétriere	Paris
France	Hôpital Saint Antoine	Paris
France	APHP - Hôpital Saint Louis	Paris Cedex 10
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	CHU de Rennes - Hôpital de Pontchaillou	Rennes
France	IUCT Oncopole	Toulouse
France	CHU Brabois	Vandoeuvre les Nancy
France	Institut de Cancérologie Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Best objective response	Percentage of CMR and Partial MR determined by investigator disease assessment	between Day 14 and Month 12
Secondary	Number of Serious Adverse Events (SAE)		at 30 days after axi-cel infusion
Secondary	Event-free survival (EFS) based on investigator disease assessment		at 3 months
Secondary	Event-free survival (EFS) based on investigator disease assessment		at 6 months
Secondary	Event-free survival (EFS) based on investigator disease assessment		at 12 months
Secondary	Event-free survival (EFS) based on central imaging review		at 3 months
Secondary	Event-free survival (EFS) based on central imaging review		at 6 months
Secondary	Event-free survival (EFS) based on central imaging review		at 12 months
Secondary	Modified EFS (mEFS) based on investigator assessment		at 6 months
Secondary	Modified EFS (mEFS) based on investigator assessment		at 12 months
Secondary	Modified EFS (mEFS) based on central imaging review		at 6 months
Secondary	Modified EFS (mEFS) based on central imaging review		at 12 months
Secondary	Best objective response		at 2 years
Secondary	Best objective response		at 3 years
Secondary	Duration of response (DOR)		at 2 years
Secondary	Duration of response (DOR)		at 3 years
Secondary	Overall survival (OS) from leukaphaeresis and Axi-cel infusion		at 2 years
Secondary	Overall survival (OS) from leukaphaeresis and Axi-cel infusion		at 3 years