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

Universität des Saarlandes

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: Lymphoma, Non-Hodgkin

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03366272

DSHNHL 2015-1

Details and patient eligibility

About

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

Full description

International, multicentre, randomised, open-label, treatment optimisation study, preceded by safety run-in phases conducted for B-cell and T-cell lymphoma separately.

Enrollment: 348 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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348 participants in 2 patient groups

(R)-GemOx

Active Comparator group

Description:

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)

Treatment:

Drug: Gemcitabine

Drug: Rituximab

Device: Oxaliplatin

Nivo-(R)-GemOx

Experimental group

Description:

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

Treatment:

Drug: Nivolumab

Drug: Gemcitabine

Drug: Rituximab

Device: Oxaliplatin