ARGO

Title

A phase II Study of Atezolizumab with Rituximab, Gemcitabine and Oxaliplatin in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma who are not candidates for High Dose Therapy

Description

ARGO is a phase II trial evaluating the addition of Atezolizumab to current therapy of Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) that are not candidates for high-dose therapy.

Objectives

Primary objective:

• To document the durable anti-tumour activity of R-GemOx-Atezo in patients with relapsed or refractory DLBCL.

Secondary objectives:

• To determine the safety and toxicity profile of R-GemOx-Atezo regimen.
• To document the anti-tumour activity of R-GemOx-Atezo in patients with relapsed or refractory DLBCL.
• To document the durability of R-GemOx-Atezo in patients with relapsed or refractory DLBCL.
• To determine the overall survival of patients treated R-GemOx-Atezo.

Tertiary objectives:

• To correlate clinical outcomes with gene expression analysis of PD-1, PD-L1, PD-L2 and other immune signatures from primary tumour material.
• To correlate clinical outcomes with immunohistochemical expression in tumour material of PD-1, PD-L1, PD-L2 and other markers in both tumour and microenvironment.
• To correlate clinical outcomes with expression of PD-1, PD-L1/L2 on peripheral blood T-cells. Sub division of T-lymphocyte sub-sets.
• To determine the profile of recurrent mutations observed in patients with DLBCL in this population and correlate to clinical response.
• To correlate clinical outcomes with known prognostic molecular features in DLBCL.
• To correlate clinical outcomes with cell of origin of DLBCL (ABC, GCB, unclassified).
• To examine use of plasma nucleic acid as a surrogate target in DLBCL and observation of dynamic change during study period.
• To examine the link between tumour-infiltrating T cell repertoire in pre-treatment biopsies and clinical outcomes.

Trial Design

This is a multicentre, randomised phase IIa trial in participants with relapsed or refractory DLBCL.

We aim to recruit 112 patients. This study will have two treatment arms.

All patients will receive one cycle of R-GemOx. Three quarters of patients (Arm B) will go on to have a further 5 cycles (every 14 days) of R-GemOx with Atezolizumab, with one quarter of patients (Arm A) continuing with 5 cycles of R-GemOx.

The patients in Arm B will continue to have Atezolizumab every 21 days for 8 cycles whilst Arm A patients will enter an observational phase during this time.

Follow up will begin at 12 months from initial treatment until month 36.

Trial Status

Open to recruitment

Population

Patients aged ≥16 years with relapsed or refractory Diffuse Large B-Cell Lymphoma that are not candidates for high-dose therapy.