Etude : ALYCANTE /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : ALYCANTE

Situation thérapeutique : Greffe

Traitement : Thérapie génique et cellulaire

Cadre réglementaire : RIPH1

Dernière MÀJ : 30/11/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Lymphome non hodgkinien à cellules B agressif en rechute ou réfractaire ne pouvant être traité par autogreffe de cellules souches : phase 2 - évaluation d’un traitement de 2e ligne par cellules CAR T Axi-Cel (Yescarta®)

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : BRIEF SUMMARY:
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 ARM:
- Experimental: axicabtagene ciloleucel
Single infusion administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg

CURRENT PRIMARY OUTCOME:
Complete Metabolic Response (CMR) from axi-cel infusion (without additional anticancer therapy) based on investigator disease assessment according to PET-scan (using the Lugano Response Criteria) [ Time Frame: 3 months from axi-cel infusion ]

CURRENT SECONDARY OUTCOME:
- Complete Metabolic Response (CMR) - determined by central imaging review [ Time Frame: 3 months from axi-cel infusion ]
- Best objective response [ Time Frame: between Day 14 and Month 12 ]
- Number of Serious Adverse Events (SAE) [ Time Frame: at 30 days after axi-cel infusion ]
- Event-free survival (EFS) based on investigator disease assessment [ Time Frame: at 3 months, at 6 months, at 12 months]
- Event-free survival (EFS) based on central imaging review [ Time Frame: at 3 months, at 6 months, at 12 months]
- Modified EFS (mEFS) based on investigator assessment [ Time Frame: at 6 months, at 12 months]
- Modified EFS (mEFS) based on central imaging review [ Time Frame: at 6 months, at 12 months]
- Best objective response [ Time Frame: at 2 years, at 3 years ]
- Duration of response (DOR) [ Time Frame: at 2 years, at 3 years ] ]
- Overall survival (OS) from leukaphaeresis and Axi-cel infusion [ Time Frame: at 2 years, at 3 years ]

Phase : II

Stade : NA

Rechute, Réfractaire
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - 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)

Critères de non-inclusion : - 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
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04531046
Promoteur :
lysarc
Type de sponsor : Institutionnel
Centre hospitalier Lyon sud, secteur sainte Eugénie, pavillon 6E
69001 LYON 01

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Statut de l'essai : OUVERT

MAJ : 25/03/2021