NCT03422523

Atezolizumab, Rituximab, Gemcitabine and Oxaliplatin in Patients With Relapsed or Refractory DLBCL Not Suitable for High-dose Therapy

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (actual)
• Sponsor: University Hospital Southampton NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates 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. 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 32.

Detailed description

Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. The R-GemOx regimen has been adopted by many sites internationally as therapy for older patients or comorbid patients with relapsed or refractory DLBCL and as a back-bone for the investigation of novel therapies in combination with chemotherapy. The cytotoxic T-lymphocyte co-receptor PD-1 has been extensively studied and is recognised to provide critical inhibitory signals that down-regulate T-cell function and provides a mechanism for immune evasion for tumours. PD-L1, the ligand of PD-1 is expressed on DLBCL tumour cells, along with infiltrating non-malignant cells, primarily macrophages, with PD-1 expressed on tumour infiltrating lymphocytes (TILs). Atezolizumab targets programmed PD-L1 on immune and tumour cells and prevents interaction with either PD-1 receptor or B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells. Interference of the PD-L1:PD-1 and PDL1:B7.1 interactions may enhance the magnitude and quality of the tumour-specific T-cell response through increased T-cell priming, expansion, and/or effector function. This study of atezolizumab in combination with rituximab, gemcitabine and oxaliplatin aims to address the unmet need of patients with relapsed and refractory DLBCL. It is based upon a sound mechanistic approach, investigating the activity of novel agents and will aim to compressively explore biomarkers of response. The primary objective will be to document the durability of anti-tumour activity in patients with relapsed or refractory DLBCL and to determine the safety and toxicity profile of the combination. A maintenance phase of atezolizumab has been added as this may induce an on-going T-cell response to neo-antigens released as a result of chemotherapy.

Conditions

• Diffuse Large B Cell Lymphoma
• Relapsed Diffuse Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Atezolizumab	Intravenous drip
DRUG	Rituximab	Intravenous drip/or Subcutaneous from cycle 2
DRUG	Gemcitabine 1000 mg	intravenous drip
DRUG	Oxaliplatin 100 MG	intravenous drip

Timeline

• Start date: 2018-05-09
• Primary completion: 2021-01-31
• Completion: 2021-11-18
• First posted: 2018-02-05
• Last updated: 2022-08-22

Locations

1 site across 1 country: United Kingdom