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
- COMPLETED
- 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 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
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
Trial Locations
- Locations (76)
Landeskrankenhaus Feldkirch
🇦🇹Feldkirch, Austria
Innsbruck University Hospital
🇦🇹Innsbruck, Austria
Kepler Universitätsklinikum GmbH- Med. Campus III
🇦🇹Linz, Austria
Ordensklinikum Linz - Elisabethinen
🇦🇹Linz, Austria
Ordensklinikum Linz - Krankenhaus der Barmherzigen Schwestern Linz
🇦🇹Linz, Austria
Paracelsus Medical University Salzburg
🇦🇹Salzburg, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Universitätsklinik für Innere Medizin I, AKH Wien
🇦🇹Wien, Austria
INSTITUT JULES BORDET -Hematology
🇧🇪Brüssel, Belgium
UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Hematology
🇧🇪Brüssel, Belgium
Scroll for more (66 remaining)Landeskrankenhaus Feldkirch🇦🇹Feldkirch, Austria