Nivolumab With Gemcitabine, Oxaliplatin + Rituximab in r/r Elderly Lymphoma Patients
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Registration Number
- NCT03366272
- Lead Sponsor
- Universität des Saarlandes
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 348
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (R)-GemOx Oxaliplatin 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) Nivo-(R)-GemOx Oxaliplatin eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first (R)-GemOx Rituximab 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) (R)-GemOx Gemcitabine 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) Nivo-(R)-GemOx Nivolumab eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first Nivo-(R)-GemOx Rituximab eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first Nivo-(R)-GemOx Gemcitabine eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
- Primary Outcome Measures
Name Time Method PFS 1 year Progression free survival
- Secondary Outcome Measures
Name Time Method Relapse rate up to 2 years after inclusion of last patient Rate of relapses
EFS up to 2 years after inclusion of last patient Event free survival
Primary Progression rate up to 2 years after inclusion of last patient Rate of Primary progression
Biological Parameters according to 9p24.1 alterations up to 2 years after inclusion of last patient Outcome assessment of response according to 9p24.1 alterations
Protocol adherence according to cumulative dose of immunochemotherapy given up to 2 years after inclusion of last patient Protocol adherence will be determined according to cumulative dose of immunochemotherapy given
QoL up to 1 year after inclusion of last patient Quality of Life (QoL) will be assessed by the EQ-5D-5L questionnaire
PR rate 4-6 weeks after cycle 8 (each cycle is 14 days) partial response rate
ORR rate 4-6 weeks after cycle 8 (each cycle is 14 days) overall response rate
Duration of response up to 2 years after inclusion of last patient Duration of response
Treatment related deaths rate up to 2 years after inclusion of last patient Rate of Treatment related deaths
Toxicities: rates and grades of adverse events up to 2 years after inclusion of last patient Toxicity: Rates and grades of toxicities will be determined according to CTC-v4.03
Protocol adherence according to duration of given chemotherapy cycles up to 2 years after inclusion of last patient Protocol adherence will be determined according to duration of chemotherapy cycles
CR rate 4-6 weeks after cycle 8 (each cycle is 14 days) complete response rate
OS up to 2 years after inclusion of last patient Overall survival
Protocol adherence according to number of given chemotherapy cycles up to 2 years after inclusion of last patient Protocol adherence will be determined according to number of chemotherapy cycles
Biological Parameters according to PD-L1 expression alterations up to 2 years after inclusion of last patient Outcome assessment of response according to PD-L1 expression alterations
Biological Parameters according to PD-1 expression up to 2 years after inclusion of last patient Outcome assessment of response according to PD-1 expression
Biological Parameters according to cell of origin up to 2 years after inclusion of last patient Outcome assessment of response according to cell of origin
Protocol adherence according to relative dose of immunochemotherapy given up to 2 years after inclusion of last patient Protocol adherence will be determined according to relative dose of immunochemotherapy given
Trial Locations
- Locations (76)
UNIVERSITE CATHOLIQUE DE LOUVAIN MONT GODINNE - Hematology
🇧🇪Yvoir, Belgium
Kepler Universitätsklinikum GmbH- Med. Campus III
🇦🇹Linz, Austria
Landeskrankenhaus Feldkirch
🇦🇹Feldkirch, Austria
Ordensklinikum Linz - Elisabethinen
🇦🇹Linz, Austria
Paracelsus Medical University Salzburg
🇦🇹Salzburg, Austria
INSTITUT JULES BORDET -Hematology
🇧🇪Brüssel, Belgium
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
UNIVERSITAIR ZIEKENHUIS GENT - Hematology
🇧🇪Gent, Belgium
CHU DE LIEGE - Hematology
🇧🇪Liège, Belgium
CHU Côte de Nacre - Service Hématologie Clinique
🇫🇷Caen, France
Hôpital Henri Mondor - Unité "Hémopathies Lymphoïdes" - HDJ 11è
🇫🇷Créteil Cedex, France
CHU Dijon - Hôpital d'Enfants - Hématologie Clinique
🇫🇷Dijon, France
CHU de Grenoble - Hôpital Albert Michallon - Hématologie Clinique
🇫🇷Grenoble, France
CH Départemental Vendée - Onco-Hématologie
🇫🇷La Roche-sur-Yon, France
Hôpital Saint Louis - Onco-Hématologie
🇫🇷Paris cedex 20, France
CHRU de Lille - Hôpital Claude Hurriez
🇫🇷Lille, France
CHU de Nantes - Hôtel Dieu - Hématologie
🇫🇷Nantes, France
Hôpital Necker - Hématologie Clinique
🇫🇷Paris, France
CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
🇫🇷Pessac, France
CHU Lyon Sud - Hématologie
🇫🇷Pierre-Bénite, France
Centre Henri Becquerel - Hématologie
🇫🇷Rouen, France
Hôpital Pontchaillou - Hématologie
🇫🇷Rennes, France
CHU Nancy - Hôpital de Brabois - Service d'Hématologie et Médecine Interne
🇫🇷Vandoeuvre-les-Nancy, France
Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
🇫🇷Strasbourg, France
Sozialstiftung Bamberg
🇩🇪Bamberg, Germany
Charité - Universitätsklinikum Berlin, Med. Klinik m. S. Hämatologie
🇩🇪Berlin, Germany
Vivantes Klinikum am Urban, Klinik für Innere, Hämatologie und Onkologie
🇩🇪Berlin, Germany
Gemeinschaftspraxis Dres. Mohm, Prange-Krex
🇩🇪Dresden, Germany
Klinikum Chemnitz, Innere Medizin III
🇩🇪Chemnitz, Germany
BAG Freiberg-Richter, Jacobasch, Wolf, Illmer
🇩🇪Dresden, Germany
Universitätsmedizin Göttingen, Klinik für Hämatologie
🇩🇪Göttingen, Germany
Universitätsklinikum Essen, Klinik für Hämatologie
🇩🇪Essen, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum des Saarlandes, Innere Med. I
🇩🇪Homburg, Germany
Universitätsklinikum Haale (Saale), Klinik für Innere Medizin IV
🇩🇪Haale, Germany
Westpfalz-Klinikum, Klinik für Innere Medizin I
🇩🇪Kaiserslautern, Germany
Uni Gießen und Marburg, Klinik für Hämatologie
🇩🇪Marburg, Germany
Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin
🇩🇪Mutlangen, Germany
Klinikum der Universität München, Med. Klinik und Poliklinik III
🇩🇪München, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Brüderkrankenhaus St. Josef Paderborn
🇩🇪Paderborn, Germany
Universitätsklinikum Regensburg, Klinik für Innere Medizin III
🇩🇪Regensburg, Germany
Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I
🇩🇪Trier, Germany
Universitätsmedizin Rostock, Klinik für Hämatologie
🇩🇪Rostock, Germany
Klinikum Stuttgart, Klinik für Hämatologie
🇩🇪Stuttgart, Germany
Universitätsklinikum Tübingen, Innere Medizin II
🇩🇪Tübingen, Germany
Krankenhaus der Barmherzigen Brüder, I. Med. Abteilung
🇩🇪Trier, Germany
Schwarzwald-Baar Klinikum, Innere Medizin II
🇩🇪Villingen-Schwenningen, Germany
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
AMC Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
VUMC
🇳🇱Amsterdam, Netherlands
MC Alkmaar
🇳🇱Alkmaar, Netherlands
Maxima Medisch Centrum
🇳🇱Eindhoven, Netherlands
MC Leeuwarden Zuid
🇳🇱Leeuwarden, Netherlands
Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Swietorkrzyskie Centrum Oncologii
🇵🇱Kielce, Poland
Szpital Specjalistyczny w Brozowie
🇵🇱Brzozów, Poland
Radboudumc Nijmegen
🇳🇱Nijmegen, Netherlands
Oncologic Center
🇵🇱Tomaszów Mazowiecki, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Marie Sklodowska-Curie Institute and Oncology
🇵🇱Warsaw, Poland
Wojskowy Instytut Medyczny
🇵🇱Warszawa, Poland
Instituto Português Oncologia - Hematology
🇵🇹Lisboa, Portugal
IUCT Oncopole - Hématologie
🇫🇷Toulouse, France
Innsbruck University Hospital
🇦🇹Innsbruck, Austria
UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Hematology
🇧🇪Brüssel, Belgium
CHU de Montpellier - Hématologie Clinique
🇫🇷Montpellier, France
Institut de Cancèrologie Lucien Neuwirth
🇫🇷Saint-Priest-en-Jarez, France
St. Antonius-Hospital Eschweiler, Klinik für Hämatologie
🇩🇪Eschweiler, Germany
St. Vincentius Kliniken Karlsruhe, Med. Klinik Abt. 2
🇩🇪Karlsruhe, Germany
Samodzielny Publiczny Szpital Kliniczny Nr. 1
🇵🇱Lublin, Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Poland
The Chaim Sheba Medical Center - Division of Hematology and Bone-Marrow Transplantation
🇮🇱Ramat Gan, Israel
Uniklinikum Ulm, Klinik für Innere Medizin III
🇩🇪Ulm, Germany
Ordensklinikum Linz - Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Universitätsklinik für Innere Medizin I, AKH Wien
🇦🇹Wien, Austria