nivolumab with gemcitabine, oxaliplatin + rituximab in r/r elderly lymphoma patients

Conditions: Lymphoma, Non-Hodgkin

Summary: 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.