Patients with first relapse or progression of aggressive Non-Hodgkin’s Lymphoma who are not eligible neither for autologous nor allogeneic stem cell transplantation MedDRA version: 22.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Saarland University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - all patient >65 years of age or > 18 years if not eligible for neither autologous nor allogeneic stem cell transplantation - >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 -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 -Performance status ECOG 0 – 2 - Patients must have only one prior chemotherapy regimen including an anthracycline. The last cytotoxic drug must be given at least four weeks prior randomization. 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 use any contraceptive method with a failure rate of less than 1% per year - Written informed consent of the patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 350
Exclusion criteria
Exclusion criteria: -Already initiated lymphoma therapy after first relapse or progression (except for the prephase Treatment) -Serious accompanying disorder or impaired organ function (except when due to lymphoma involvement) -WBC 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 -Patients with an active, known or suspected autoimmune disease -no requirement for immunosuppressive doses of systemic corticosteroids (except for treatment of lymphoma) -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 (intracerebral, meningeal, intraspinal intradural) or primary CNS lymphoma - Persistent neuropathy grade >2 (NCI CTC-AE v4.03) (unless due to lymphoma involvement) -Pregnancy or breast-feeding women - Women of childbearing potential (WOCBP) - Active serious infections not controlled by oral and/or intravenous antibiotics or antifungal 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Improvement of 1-yr PFS by nivolumab plus (R)-GemOx followed by nivolumab consolidation instead of (R)-GemOx alone in patients with progressed or relapsed aggressive NHLs not eligible neither for autologous nor allogeneic stem cell transplantation;Secondary Objective: ?- To determine whether survival can be increased by adding nivolumab to standard (R)-GemOx. ?- To determine whether outcome can be improved by adding nivolumab to standard (R)-GemOx. ?- To determine toxicity and protocol adherence of standard (R)-GemOx with or without nivolumab. ?- To evaluate quality of life of patients with relapsed or refractory aggressive Non-Hodgkin’s Lymphoma treated with (R)-GemOx with or without Nivolumab. ?- To analyze outcome according to biological parameters. ;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: 1 year (data collected during the restagings and the follow-up assessments as planned in the protocol (cf. chapter 8.9 in the protocol)) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •complete response rate •partial response rate •overall response rate •duration of response •progression rate •rate of treatment-related deaths •relapse rate •Event-free survival •Overall survival •Toxicity •Protocol adherence •quality of life as assessed by the EQ-5D-5L. •outcome according to PD-L1 and PD-1 expression, cell of origin, 9p24.1 alterations ;Timepoint(s) of evaluation of this end point: •complete response rate , partial response rate, overall response rate : (data collected during the restagings and the follow-up assessments as planned in the protocol (cf. chapter 8.9 in the protocol)) •duration of response : end of study •progression rate : end of study •rate of treatment-related deaths : end of study •relapse rate : end of study •Event-free survival : end of study •Overall survival : end of study •Toxicity : end of study •Protocol adherence : end of study •quality of life as assessed by the EQ-5D-5L : end of study •outcome according to PD-L1 and PD-1 expression, cell of origin, 9p24.1 alterations : end of study (data collected during the restagings and the follow-up assessments as planned in the protocol (cf. chapter 8.9 in the protocol)) | — |
Countries
Austria, Belgium, Czechia, France, Germany, Israel, Netherlands, Poland, Portugal
Contacts
Public ContactKlinik fuer Innere Medizin I
DSHNHL / GLA
Outcome results
None listed