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

Phase 2
Active, not recruiting
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
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
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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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
(R)-GemOxOxaliplatineight 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)-GemOxOxaliplatineight 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)-GemOxRituximabeight 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)-GemOxGemcitabineeight 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)-GemOxNivolumabeight 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)-GemOxRituximabeight 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)-GemOxGemcitabineeight 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
NameTimeMethod
PFS1 year

Progression free survival

Secondary Outcome Measures
NameTimeMethod
Relapse rateup to 2 years after inclusion of last patient

Rate of relapses

EFSup to 2 years after inclusion of last patient

Event free survival

Primary Progression rateup to 2 years after inclusion of last patient

Rate of Primary progression

Biological Parameters according to 9p24.1 alterationsup 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 givenup to 2 years after inclusion of last patient

Protocol adherence will be determined according to cumulative dose of immunochemotherapy given

QoLup to 1 year after inclusion of last patient

Quality of Life (QoL) will be assessed by the EQ-5D-5L questionnaire

PR rate4-6 weeks after cycle 8 (each cycle is 14 days)

partial response rate

ORR rate4-6 weeks after cycle 8 (each cycle is 14 days)

overall response rate

Duration of responseup to 2 years after inclusion of last patient

Duration of response

Treatment related deaths rateup to 2 years after inclusion of last patient

Rate of Treatment related deaths

Toxicities: rates and grades of adverse eventsup 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 cyclesup to 2 years after inclusion of last patient

Protocol adherence will be determined according to duration of chemotherapy cycles

CR rate4-6 weeks after cycle 8 (each cycle is 14 days)

complete response rate

OSup to 2 years after inclusion of last patient

Overall survival

Protocol adherence according to number of given chemotherapy cyclesup 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 alterationsup to 2 years after inclusion of last patient

Outcome assessment of response according to PD-L1 expression alterations

Biological Parameters according to PD-1 expressionup to 2 years after inclusion of last patient

Outcome assessment of response according to PD-1 expression

Biological Parameters according to cell of originup 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 givenup 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

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