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Lymphoma, Non-HodgkinPhase 2/3NIVEAUNCT03366272

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

A Phase 2/3 study testing Nivolumab, Rituximab and Gemcitabine in people with Lymphoma, Non-Hodgkin, run by Universität des Saarlandes at 77 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study evaluates the addition of nivolumab to gemcitabine, oxaliplatin plus rituximab in case of B-cell lymphoma Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
Nivolumab, Rituximab and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
348 participants
Where
77 sitesin 8 countries
Study dates
5 Dec 2017to 15 Jan 2025
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

77 sites in 8 countries.

77 sites in 8 countries

Germany27 sites
  • Sozialstiftung Bamberg

    Bamberg

  • Charité - Universitätsklinikum Berlin, Med. Klinik m. S. Hämatologie

    Berlin

  • Vivantes Klinikum am Urban, Klinik für Innere, Hämatologie und Onkologie

    Berlin

  • Klinikum Chemnitz, Innere Medizin III

    Chemnitz

  • BAG Freiberg-Richter, Jacobasch, Wolf, Illmer

    Dresden

  • Gemeinschaftspraxis Dres. Mohm, Prange-Krex

    Dresden

  • St. Antonius-Hospital Eschweiler, Klinik für Hämatologie

    Eschweiler

  • Universitätsklinikum Essen, Klinik für Hämatologie

    Essen

  • Universitätsmedizin Göttingen, Klinik für Hämatologie

    Göttingen

  • Universitätsklinikum Haale (Saale), Klinik für Innere Medizin IV

    Haale

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

  • Universitätsklinikum des Saarlandes, Innere Med. I

    Homburg

  • Westpfalz-Klinikum, Klinik für Innere Medizin I

    Kaiserslautern

  • St. Vincentius Kliniken Karlsruhe, Med. Klinik Abt. 2

    Karlsruhe

  • Uni Gießen und Marburg, Klinik für Hämatologie

    Marburg

  • Klinikum der Universität München, Med. Klinik und Poliklinik III

    München

  • Universitätsklinikum Münster

    Münster

  • Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin

    Mutlangen

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn

  • Universitätsklinikum Regensburg, Klinik für Innere Medizin III

    Regensburg

  • Universitätsmedizin Rostock, Klinik für Hämatologie

    Rostock

  • Klinikum Stuttgart, Klinik für Hämatologie

    Stuttgart

  • Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I

    Trier

  • Krankenhaus der Barmherzigen Brüder, I. Med. Abteilung

    Trier

  • Universitätsklinikum Tübingen, Innere Medizin II

    Tübingen

  • Uniklinikum Ulm, Klinik für Innere Medizin III

    Ulm

  • Schwarzwald-Baar Klinikum, Innere Medizin II

    Villingen-Schwenningen

Other trials in Germany

France18 sites
  • CHU Côte de Nacre - Service Hématologie Clinique

    Caen

  • Hôpital Henri Mondor - Unité "Hémopathies Lymphoïdes" - HDJ 11è

    Créteil

  • CHU Dijon - Hôpital d'Enfants - Hématologie Clinique

    Dijon

  • CHU de Grenoble - Hôpital Albert Michallon - Hématologie Clinique

    Grenoble

  • CH Départemental Vendée - Onco-Hématologie

    La Roche-sur-Yon

  • CHRU de Lille - Hôpital Claude Hurriez

    Lille

  • CHU de Montpellier - Hématologie Clinique

    Montpellier

  • CHU de Nantes - Hôtel Dieu - Hématologie

    Nantes

  • Hôpital Necker - Hématologie Clinique

    Paris

  • Hôpital Saint Louis - Onco-Hématologie

    Paris

  • CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie

    Pessac

  • CHU Lyon Sud - Hématologie

    Pierre-Bénite

  • Hôpital Pontchaillou - Hématologie

    Rennes

  • Centre Henri Becquerel - Hématologie

    Rouen

  • Institut de Cancèrologie Lucien Neuwirth

    Saint-Priest-en-Jarez, 42271

  • Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

    Strasbourg

  • IUCT Oncopole - Hématologie

    Toulouse

  • CHU Nancy - Hôpital de Brabois - Service d'Hématologie et Médecine Interne

    Vandœuvre-lès-Nancy

Other trials in France

Poland9 sites
  • Szpital Specjalistyczny w Brozowie

    Brzozów

  • Oncologic Center

    Bydgoszcz

  • Uniwersyteckie Centrum Kliniczne

    Gdansk

  • Swietorkrzyskie Centrum Oncologii

    Kielce

  • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

    Krakow

  • Samodzielny Publiczny Szpital Kliniczny Nr. 1

    Lublin

  • Oncologic Center

    Tomaszów Mazowiecki

  • Marie Sklodowska-Curie Institute and Oncology

    Warsaw

  • Wojskowy Instytut Medyczny

    Warsaw

Other trials in Poland

Austria8 sites
  • Landeskrankenhaus Feldkirch

    Feldkirch

  • Innsbruck University Hospital

    Innsbruck

  • Kepler Universitätsklinikum GmbH- Med. Campus III

    Linz

  • Ordensklinikum Linz - Elisabethinen

    Linz

  • Ordensklinikum Linz - Krankenhaus der Barmherzigen Schwestern Linz

    Linz

  • Paracelsus Medical University Salzburg

    Salzburg

  • Universitätsklinik für Innere Medizin I, AKH Wien

    Vienna

  • Klinikum Wels-Grieskirchen GmbH

    Wels

Other trials in Austria

Netherlands8 sites
  • MC Alkmaar

    Alkmaar

  • AMC Academisch Medisch Centrum

    Amsterdam

  • VUMC

    Amsterdam

  • Reinier de Graaf Gasthuis

    Delft

  • Maxima Medisch Centrum

    Eindhoven

  • MC Leeuwarden Zuid

    Leeuwarden

  • Antonius Ziekenhuis

    Nieuwegein

  • Radboudumc Nijmegen

    Nijmegen

Other trials in Netherlands

Belgium5 sites
  • INSTITUT JULES BORDET -Hematology

    Brussels

  • UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Hematology

    Brussels

  • UNIVERSITAIR ZIEKENHUIS GENT - Hematology

    Ghent

  • CHU DE LIEGE - Hematology

    Liège

  • UNIVERSITE CATHOLIQUE DE LOUVAIN MONT GODINNE - Hematology

    Yvoir

Other trials in Belgium

Israel1 site
  • The Chaim Sheba Medical Center - Division of Hematology and Bone-Marrow Transplantation

    Ramat Gan

Other trials in Israel

Portugal1 site
  • Instituto Português Oncologia - Hematology

    Lisbon

Other trials in Portugal

About this study

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

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

Read the 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.

Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    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

  • RituximabDrug

    eight cycles of R-GemOx in 2-wk intervals

  • GemcitabineDrug

    eight cycles of (R)-GemOx in 2-wk intervals

  • OxaliplatinDevice

    eight cycles of (R)-GemOx in 2-wk intervals

Study groups in NCT03366272
Study groupRoleWhat they receive
(R)-GemOxActive comparatoreight 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)
Receives: Drug: Rituximab; Drug: Gemcitabine; Device: Oxaliplatin
Nivo-(R)-GemOxExperimentaleight 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
Receives: Drug: Nivolumab; Drug: Rituximab; Drug: Gemcitabine; Device: Oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PFS

    Progression free survival

    Measured: 1 year

Secondary outcomes (19)
  1. CR rate

    complete response rate

    Measured: 4-6 weeks after cycle 8 (each cycle is 14 days)

  2. PR rate

    partial response rate

    Measured: 4-6 weeks after cycle 8 (each cycle is 14 days)

  3. ORR rate

    overall response rate

    Measured: 4-6 weeks after cycle 8 (each cycle is 14 days)

  4. Duration of response

    Duration of response

    Measured: up to 2 years after inclusion of last patient

  5. Primary Progression rate

    Rate of Primary progression

    Measured: up to 2 years after inclusion of last patient

  6. Treatment related deaths rate

    Rate of Treatment related deaths

    Measured: up to 2 years after inclusion of last patient

  7. Relapse rate

    Rate of relapses

    Measured: up to 2 years after inclusion of last patient

  8. EFS

    Event free survival

    Measured: up to 2 years after inclusion of last patient

  9. OS

    Overall survival

    Measured: up to 2 years after inclusion of last patient

  10. Toxicities: rates and grades of adverse events

    Toxicity: Rates and grades of toxicities will be determined according to CTC-v4.03

    Measured: up to 2 years after inclusion of last patient

  11. Protocol adherence according to number of given chemotherapy cycles

    Protocol adherence will be determined according to number of chemotherapy cycles

    Measured: up to 2 years after inclusion of last patient

  12. Protocol adherence according to duration of given chemotherapy cycles

    Protocol adherence will be determined according to duration of chemotherapy cycles

    Measured: up to 2 years after inclusion of last patient

  13. Protocol adherence according to cumulative dose of immunochemotherapy given

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

    Measured: up to 2 years after inclusion of last patient

  14. Protocol adherence according to relative dose of immunochemotherapy given

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

    Measured: up to 2 years after inclusion of last patient

  15. QoL

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

    Measured: up to 1 year after inclusion of last patient

  16. Biological Parameters according to PD-L1 expression alterations

    Outcome assessment of response according to PD-L1 expression alterations

    Measured: up to 2 years after inclusion of last patient

  17. Biological Parameters according to PD-1 expression

    Outcome assessment of response according to PD-1 expression

    Measured: up to 2 years after inclusion of last patient

  18. Biological Parameters according to cell of origin

    Outcome assessment of response according to cell of origin

    Measured: up to 2 years after inclusion of last patient

  19. Biological Parameters according to 9p24.1 alterations

    Outcome assessment of response according to 9p24.1 alterations

    Measured: up to 2 years after inclusion of last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2017
  2. Study start5 Dec 2017
  3. Primary completion15 Jan 2025
  4. Study completion15 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
348 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03366272
Sponsor's protocol ID
DSHNHL 2015-1
Acronym
NIVEAU
Status last verified
Jan 2025
First submitted
16 Sep 2017
Last updated
28 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Nivolumab, Rituximab and Gemcitabine in people with Lymphoma, Non-Hodgkin, run by Universität des Saarlandes at 77 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in Germany, France, Poland, Austria, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.

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