Etude : NIVEAU /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : NIVEAU

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 27/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Improvement of Outcome in Elderly Patients or Patients Not Eligible for High-dose Chemotherapy With Aggressive NHL in First Relapse/Progression by Adding Nivolumab to Gemcitabine, Oxaliplatin Plus Rituximab in Case of B-cell Lymphoma

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 : International, multicentre, randomised, open-label, treatment optimisation study, preceded by safety run-in phases conducted for B-cell and T-cell lymphoma separately.

Study arms:
- Active Comparator: (R)-GemOx
eight cycles of (R)-GemOx (Gemcitabine 1000 mg/m2, d1, Oxaliplatin 100 mg/m2, d1, Rituximab 375 mg/m2 in case of B-cell lymphoma disease, repeated every 2 wks)
Interventions:
Drug: Rituximab
Drug: Gemcitabine
Device: Oxaliplatin
- Experimental: Nivo-(R)-GemOx
eight cycles of nivolumab (3 mg/kg) plus (R)-GemOx in 2-wk intervals followed by additional 18 infusions of Nivolumab (3 mg/kg) in 2-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
Interventions:
Drug: Nivolumab
Drug: Rituximab
Drug: Gemcitabine
Device: Oxaliplatin

Current primary outcome:
Progression Free Survival [ Time Frame: 1 year ]

Current secondary outcomes:
- Complete Response rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
- Partial Response rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
- Overall Response Rate [ Time Frame: 4-6 weeks after cycle 8 (each cycle is 14 days) ]
- Duration of response [ Time Frame: up to 2 years after inclusion of last patient ]
- Primary Progression rate [ Time Frame: up to 2 years after inclusion of last patient ]
- Treatment related deaths rate [ Time Frame: up to 2 years after inclusion of last patient ]
- Relapse rate [ Time Frame: up to 2 years after inclusion of last patient ]
- Event Free Survival [ Time Frame: up to 2 years after inclusion of last patient ]
- Overall Survival [ Time Frame: up to 2 years after inclusion of last patient ]
- Toxicities: rates and grades of adverse events [ Time Frame: up to 2 years after inclusion of last patient ]
- Protocol adherence according to number of given chemotherapy cycles [ Time Frame: up to 2 years after inclusion of last patient ]
- Protocol adherence according to duration of given chemotherapy cycles [ Time Frame: up to 2 years after inclusion of last patient ]
- Protocol adherence according to cumulative dose of immunochemotherapy given [ Time Frame: up to 2 years after inclusion of last patient ]
- Protocol adherence according to relative dose of immunochemotherapy given [ Time Frame: up to 2 years after inclusion of last patient ]
- QoL [ Time Frame: up to 1 year after inclusion of last patient ]
- Biological Parameters according to PD-L1 expression alterations [ Time Frame: up to 2 years after inclusion of last patient ]
- Biological Parameters according to PD-1 expression [ Time Frame: up to 2 years after inclusion of last patient ]
- Biological Parameters according to cell of origin [ Time Frame: up to 2 years after inclusion of last patient ]
- Biological Parameters according to 9p24.1 alterations [ Time Frame: up to 2 years after inclusion of last patient ]

Phase : II/III

Stade : NA

2
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 : - patients with first relapse or progression of an aggressive Non-Hodgkin's lymphoma
- all patient >65 years of age or older than 18 years if HCT-CI score > 2 or patients who underwent prior autologous stem cell transplantation and are not eligible for allogeneic stem cell Transplantation
- All risk groups (IPI 0 to 5)
- Diagnosis of aggressive Non-Hodgkin's lymphoma, based on an excisional biopsy of a lymph node or on an appropriate sample of a lymph node or of an extranodal involvement at initial diagnosis or relapse or Progression. The entities treated in the study will be based on the WHO 2017 classification.
- ECOG 0 - 2
- only one prior chemotherapy regimen including an anthracycline. The last cytotoxic drug must be given at least four weeks before entering the study. Rituximab must be part of the first-line regimen in case of B-cell lymphoma. Patients may have received prior radiation therapy as part of their first-line therapy
- Men who are sexually active with women of childbearing potential (WOCBP) must not father a child during and up to 6 months after GemOx and up to 12 months after Rituximab and/or Nivolumab. They are advised to do cryoconservation of sperm prior to treatment.
- Written informed consent of the patient
- Patient must be covered by social security system

Critères de non-inclusion : - Already initiated lymphoma therapy after first relapse or progression
- Serious accompanying disorder or impaired organ function
- WBC < 2.5 G/l, Neutrophils < 2 G/l, Platelets < 100 G/l
- Prolongation of QTc interval > 450 ms, demonstrated in one electrocardiogram (done as triplicate). This does not apply for patients with a block of the right and/or left bundle branch.
- Family history for Long QT-Syndrome
- active, known or suspected autoimmune disease
- no requirement for immunosuppressive doses of systemic corticosteroids
- Chronic active hepatitis B or C
- HIV-infection
- Patients with a severe immunodeficiency
- Previous therapy with Nivolumab,Gemcitabine or Oxaliplatin
- Patients with a "currently active" second malignancy other than non-melanoma skin cancer
- CNS involvement of lymphoma
- Persistent neuropathy grade >2
- Pregnancy or breast-feeding women
- Women of childbearing potential
- Active serious infections not controlled by oral and/or intravenous antibiotics or anti-fungal medication
- Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities
- Lymphomas other than those listed in the inclusion criteria notably indolent lymphoma, Mantle cell lymphoma, Burkitt lymphoma, adult T-cell leukemia/lymphoma.
- Persons not able to understand the impact, nature, risks and consequences of the trial (including language barrier)
- Persons not agreeing to the transmission of their pseudonymous data
- Persons depending on sponsor or investigator
- Persons from highly protected Groups
- Allergies and Adverse Drug Reaction History to study drug components
- Participation in another clinical trial with drug intervention within 4 weeks prior to start of the first cycle and during the study. However, participation in a clinical trial of firstline therapy of lymphoma is allowed.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03366272
Promoteur :
Saarland University Hospital, Germany
Type de sponsor : Institutionnel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Henri Becquerel - Rue d'Amiens CS 11516 - Cedex 1 - 76000 ROUEN

Investigateur :
Hervé TILLY

TEC / ARC / IDE :
Laure SULPLICE
laure.sulpice@
chb.unicancer.fr
02.76.67.30.52

Ouverture de l'essai : OUVERT

MAJ : 27/09/2019