Clinical trial NCT03366272: Nivolumab With Gemcitabine, Oxaliplatin + Rituximab in r/r Elderly Lymphoma Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Lymphoma, Non-Hodgkin
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Lymphoma Study Association
name: University of Leipzig
First posted: 2017-12-08
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Primary outcomes:
measure: PFS
timeFrame: 1 year
Secondary outcomes:
measure: CR rate
timeFrame: 4-6 weeks after cycle 8 (each cycle is 14 days)
measure: PR rate
timeFrame: 4-6 weeks after cycle 8 (each cycle is 14 days)
measure: ORR rate
timeFrame: 4-6 weeks after cycle 8 (each cycle is 14 days)
measure: Duration of response
timeFrame: up to 2 years after inclusion of last patient
measure: Primary Progression rate
timeFrame: up to 2 years after inclusion of last patient
measure: Treatment related deaths rate
timeFrame: up to 2 years after inclusion of last patient
measure: Relapse rate
timeFrame: up to 2 years after inclusion of last patient
measure: EFS
timeFrame: up to 2 years after inclusion of last patient
measure: OS
timeFrame: up to 2 years after inclusion of last patient
measure: Toxicities: rates and grades of adverse events
timeFrame: up to 2 years after inclusion of last patient
measure: Protocol adherence according to number of given chemotherapy cycles
timeFrame: up to 2 years after inclusion of last patient
measure: Protocol adherence according to duration of given chemotherapy cycles
timeFrame: up to 2 years after inclusion of last patient
measure: Protocol adherence according to cumulative dose of immunochemotherapy given
timeFrame: up to 2 years after inclusion of last patient
measure: Protocol adherence according to relative dose of immunochemotherapy given
timeFrame: up to 2 years after inclusion of last patient
measure: QoL
timeFrame: up to 1 year after inclusion of last patient
measure: Biological Parameters according to PD-L1 expression alterations
timeFrame: up to 2 years after inclusion of last patient
measure: Biological Parameters according to PD-1 expression
timeFrame: up to 2 years after inclusion of last patient
measure: Biological Parameters according to cell of origin
timeFrame: up to 2 years after inclusion of last patient
measure: Biological Parameters according to 9p24.1 alterations
timeFrame: up to 2 years after inclusion of last patient
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Innsbruck
country: Austria
facility: Innsbruck University Hospital
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH- Med. Campus III
city: Linz
country: Austria
facility: Ordensklinikum Linz - Elisabethinen
city: Linz
country: Austria
facility: Ordensklinikum Linz - Krankenhaus der Barmherzigen Schwestern Linz
city: Salzburg
country: Austria
facility: Paracelsus Medical University Salzburg
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: Universitätsklinik für Innere Medizin I, AKH Wien
city: Brüssel
country: Belgium
facility: INSTITUT JULES BORDET -Hematology
city: Brüssel
country: Belgium
facility: UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Hematology
city: Gent
country: Belgium
facility: UNIVERSITAIR ZIEKENHUIS GENT - Hematology
city: Liège
country: Belgium
facility: CHU DE LIEGE - Hematology
city: Yvoir
country: Belgium
facility: UNIVERSITE CATHOLIQUE DE LOUVAIN MONT GODINNE - Hematology
city: Caen
country: France
facility: CHU Côte de Nacre - Service Hématologie Clinique
city: Créteil Cedex
country: France
facility: Hôpital Henri Mondor - Unité "Hémopathies Lymphoïdes" - HDJ 11è
city: Dijon
country: France
facility: CHU Dijon - Hôpital d'Enfants - Hématologie Clinique
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon - Hématologie Clinique
city: La Roche-sur-Yon
country: France
facility: CH Départemental Vendée - Onco-Hématologie
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Hurriez
city: Montpellier
country: France
facility: CHU de Montpellier - Hématologie Clinique
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu - Hématologie
city: Paris cedex 20
country: France
facility: Hôpital Saint Louis - Onco-Hématologie
city: Paris
country: France
facility: Hôpital Necker - Hématologie Clinique
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud - Hématologie
city: Rennes
country: France
facility: Hôpital Pontchaillou - Hématologie
city: Rouen
country: France
facility: Centre Henri Becquerel - Hématologie
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancèrologie Lucien Neuwirth
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
city: Toulouse
country: France
facility: IUCT Oncopole - Hématologie
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy - Hôpital de Brabois - Service d'Hématologie et Médecine Interne
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg
city: Berlin
country: Germany
facility: Charité - Universitätsklinikum Berlin, Med. Klinik m. S. Hämatologie
city: Berlin
country: Germany
facility: Vivantes Klinikum am Urban, Klinik für Innere, Hämatologie und Onkologie
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz, Innere Medizin III
city: Dresden
country: Germany
facility: BAG Freiberg-Richter, Jacobasch, Wolf, Illmer
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Dres. Mohm, Prange-Krex
city: Eschweiler
country: Germany
facility: St. Antonius-Hospital Eschweiler, Klinik für Hämatologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hämatologie
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Klinik für Hämatologie
city: Haale
country: Germany
facility: Universitätsklinikum Haale (Saale), Klinik für Innere Medizin IV
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes, Innere Med. I
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum, Klinik für Innere Medizin I
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken Karlsruhe, Med. Klinik Abt. 2
city: Marburg
country: Germany
facility: Uni Gießen und Marburg, Klinik für Hämatologie
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin
city: München
country: Germany
facility: Klinikum der Universität München, Med. Klinik und Poliklinik III
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef Paderborn
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik für Innere Medizin III
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Klinik für Hämatologie
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart, Klinik für Hämatologie
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder, I. Med. Abteilung
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Innere Medizin II
city: Ulm
country: Germany
facility: Uniklinikum Ulm, Klinik für Innere Medizin III
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum, Innere Medizin II
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center - Division of Hematology and Bone-Marrow Transplantation
city: Alkmaar
country: Netherlands
facility: MC Alkmaar
city: Amsterdam
country: Netherlands
facility: AMC Academisch Medisch Centrum
city: Amsterdam
country: Netherlands
facility: VUMC
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Leeuwarden
country: Netherlands
facility: MC Leeuwarden Zuid
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboudumc Nijmegen
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brozowie
city: Bydgoszcz
country: Poland
facility: Oncologic Center
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kielce
country: Poland
facility: Swietorkrzyskie Centrum Oncologii
city: Kraków
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr. 1
city: Tomaszów Mazowiecki
country: Poland
facility: Oncologic Center
city: Warsaw
country: Poland
facility: Marie Sklodowska-Curie Institute and Oncology
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Lisboa
country: Portugal
facility: Instituto Português Oncologia - Hematology
Study officials:
affiliation: Universität des Saarlandes
name: Gerhard Held, Prof
role: PRINCIPAL_INVESTIGATOR
References: