Nivolumab With Gemcitabine, Oxaliplatin + Rituximab in r/r Elderly Lymphoma Patients

This study evaluates the addition of nivolumab to gemcitabine, oxaliplatin plus rituximab in case of B-cell lymphoma

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

Eligibility Criteria:
Inclusion Criteria:

* patients with first relapse or progression of an aggressive Non-Hodgkin's lymphoma
* all patient \>65 years of age or \> 18 years if not eligible for neither autologous nor allogeneic stem cell transplantation
* 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 (except for primary CD20- negative 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

Exclusion Criteria:

* 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.