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

NCT03366272 | Completed Phase 2 DMC

• 1 other identifier: DSHNHL 2015-1
• Study Type: interventional
• Target: 348
• Locations: 8 countries
• Sites: 77

Brief Summary

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

Conditions

Lymphoma, Non-Hodgkin

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression free survival

  1 year

Secondary Outcomes (19)

• CR rate

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

• PR rate

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

• ORR rate

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

• Duration of response

  up to 2 years after inclusion of last patient

• Primary Progression rate

  up to 2 years after inclusion of last patient

Study Arms (2)

(R)-GemOx

ACTIVE COMPARATOR

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)

Drug: Rituximab; Drug: Gemcitabine; Device: Oxaliplatin

Nivo-(R)-GemOx

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Rituximab; Drug: Gemcitabine; Device: Oxaliplatin

Interventions

Nivolumab DRUG

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 DRUG

eight cycles of R-GemOx in 2-wk intervals

(R)-GemOx; Nivo-(R)-GemOx

Gemcitabine DRUG

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

(R)-GemOx; Nivo-(R)-GemOx

Oxaliplatin DEVICE

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

(R)-GemOx; Nivo-(R)-GemOx

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universität des Saarlandes: lead
• Bristol-Myers Squibb: collaborator
• Lymphoma Study Association: collaborator
• University of Leipzig: collaborator

Study Sites (77)

Landeskrankenhaus Feldkirch

Feldkirch, Austria

Location

Innsbruck University Hospital

Innsbruck, Austria

Location

Kepler Universitätsklinikum GmbH- Med. Campus III

Linz, Austria

Location

Ordensklinikum Linz - Elisabethinen

Linz, Austria

Location

Ordensklinikum Linz - Krankenhaus der Barmherzigen Schwestern Linz

Linz, Austria

Location

Paracelsus Medical University Salzburg

Salzburg, Austria

Location

Universitätsklinik für Innere Medizin I, AKH Wien

Vienna, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, Austria

Location

INSTITUT JULES BORDET -Hematology

Brussels, Belgium

Location

UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Hematology

Brussels, Belgium

Location

UNIVERSITAIR ZIEKENHUIS GENT - Hematology

Ghent, Belgium

Location

CHU DE LIEGE - Hematology

Liège, Belgium

Location

UNIVERSITE CATHOLIQUE DE LOUVAIN MONT GODINNE - Hematology

Yvoir, Belgium

Location

CHU Côte de Nacre - Service Hématologie Clinique

Caen, France

Location

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

Créteil, France

Location

CHU Dijon - Hôpital d'Enfants - Hématologie Clinique

Dijon, France

Location

CHU de Grenoble - Hôpital Albert Michallon - Hématologie Clinique

Grenoble, France

Location

CH Départemental Vendée - Onco-Hématologie

La Roche-sur-Yon, France

Location

CHRU de Lille - Hôpital Claude Hurriez

Lille, France

Location

CHU de Montpellier - Hématologie Clinique

Montpellier, France

Location

CHU de Nantes - Hôtel Dieu - Hématologie

Nantes, France

Location

Hôpital Necker - Hématologie Clinique

Paris, France

Location

Hôpital Saint Louis - Onco-Hématologie

Paris, France

Location

CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie

Pessac, France

Location

CHU Lyon Sud - Hématologie

Pierre-Bénite, France

Location

Hôpital Pontchaillou - Hématologie

Rennes, France

Location

Centre Henri Becquerel - Hématologie

Rouen, France

Location

Institut de Cancèrologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42271, France

Location

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Strasbourg, France

Location

IUCT Oncopole - Hématologie

Toulouse, France

Location

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

Vandœuvre-lès-Nancy, France

Location

Sozialstiftung Bamberg

Bamberg, Germany

Location

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

Berlin, Germany

Location

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

Berlin, Germany

Location

Klinikum Chemnitz, Innere Medizin III

Chemnitz, Germany

Location

BAG Freiberg-Richter, Jacobasch, Wolf, Illmer

Dresden, Germany

Location

Gemeinschaftspraxis Dres. Mohm, Prange-Krex

Dresden, Germany

Location

St. Antonius-Hospital Eschweiler, Klinik für Hämatologie

Eschweiler, Germany

Location

Universitätsklinikum Essen, Klinik für Hämatologie

Essen, Germany

Location

Universitätsmedizin Göttingen, Klinik für Hämatologie

Göttingen, Germany

Location

Universitätsklinikum Haale (Saale), Klinik für Innere Medizin IV

Haale, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitätsklinikum des Saarlandes, Innere Med. I

Homburg, Germany

Location

Westpfalz-Klinikum, Klinik für Innere Medizin I

Kaiserslautern, Germany

Location

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

Karlsruhe, Germany

Location

Uni Gießen und Marburg, Klinik für Hämatologie

Marburg, Germany

Location

Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin

Mutlangen, Germany

Location

Klinikum der Universität München, Med. Klinik und Poliklinik III

München, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Brüderkrankenhaus St. Josef Paderborn

Paderborn, Germany

Location

Universitätsklinikum Regensburg, Klinik für Innere Medizin III

Regensburg, Germany

Location

Universitätsmedizin Rostock, Klinik für Hämatologie

Rostock, Germany

Location

Klinikum Stuttgart, Klinik für Hämatologie

Stuttgart, Germany

Location

Klinikum Mutterhaus der Borromäerinnen, Med. Abteilung I

Trier, Germany

Location

Krankenhaus der Barmherzigen Brüder, I. Med. Abteilung

Trier, Germany

Location

Universitätsklinikum Tübingen, Innere Medizin II

Tübingen, Germany

Location

Uniklinikum Ulm, Klinik für Innere Medizin III

Ulm, Germany

Location

Schwarzwald-Baar Klinikum, Innere Medizin II

Villingen-Schwenningen, Germany

Location

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

Ramat Gan, Israel

Location

MC Alkmaar

Alkmaar, Netherlands

Location

AMC Academisch Medisch Centrum

Amsterdam, Netherlands

Location

VUMC

Amsterdam, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, Netherlands

Location

MC Leeuwarden Zuid

Leeuwarden, Netherlands

Location

Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Radboudumc Nijmegen

Nijmegen, Netherlands

Location

Szpital Specjalistyczny w Brozowie

Brzozów, Poland

Location

Oncologic Center

Bydgoszcz, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Location

Swietorkrzyskie Centrum Oncologii

Kielce, Poland

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

Krakow, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr. 1

Lublin, Poland

Location

Oncologic Center

Tomaszów Mazowiecki, Poland

Location

Marie Sklodowska-Curie Institute and Oncology

Warsaw, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, Poland

Location

Instituto Português Oncologia - Hematology

Lisbon, Portugal

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Nivolumab; Rituximab; Gemcitabine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gerhard Held, Prof

  Universität des Saarlandes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2017
• First Posted: December 8, 2017
• Study Start: December 5, 2017
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

NL (8); BE (5); AU (8); IL (1); DE (27); PL (9); PT (1); FR (18)