Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Gemcitabine

Rituximab

Oxaliplatin

Atezolizumab

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

Immune Checkpoint Inhibitors

6 Cycles of R-GemOx (Rituximab, Gemcitabine and Oxaliplatin) every 14 days.

1 Cycle of R-GemOx (Rituximab, Gemcitabine and Oxaliplatin) followed by 5 cycles of R-GemOx with Atezolizumab every 14 days.

Followed by 8 maintenance cycles of Atezolizumab every 21 days.

Intravenous drip/or Subcutaneous from cycle 2

Gemcitabine 1000 mg

Oxaliplatin 100 MG

Andy Davies

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.

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.

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

Gene expression profiling on FFPE tumour material

immunohistochemical analysis of primary tumour material

flow cytometry of t-cells in peripheral blood collected during therapy

Application genes of NGS DLBCL mutation panel of 54 genes to tumour material

Examine translocations of Myc, Bcl6 and Bcl2 by FISH

Immunohistochemical analysis for dual protein expression on Myc and Bcl2

Plasma lymphoma nucleic acid at baseline studied and compared with paired lymphoma tissue sample and repeated throughout study period to examine dynamics of change and possible assessment of minimal residual disease, depending upon responses observed

Progression free survival will be measured from patient notes, from the day of registration to the date of progression or death from any cause. Patients who do not die will be censored at their date of last follow up.

Determining the toxicity and causality of each adverse event with R-GemOx-Atezo.

Objective response, partial or complete metabolic response, to be assessed by PET / CT according to LYRIC.

Overall survival will be measured from patient notes, from the day of registration to the date of death from any cause. Patients who do not die will be censored at their date of last follow up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Atezolizumab, Rituximab, Gemcitabine and Oxaliplatin in Patients With Relapsed or Refractory DLBCL Not Suitable for High-dose Therapy	NCT03422523	Diffuse Large B... Relapsed Diffus... Refractory Diff...	Atezolizumab Rituximab Gemcitabine 100... Oxaliplatin 100...	16 Years -	University Hospital Southampton NHS Foundation Trust
Atezolizumab, Rituximab, Gemcitabine and Oxaliplatin in Patients With Relapsed or Refractory DLBCL Not Suitable for High-dose Therapy	NCT03422523	Diffuse Large B... Relapsed Diffus... Refractory Diff...	Atezolizumab Rituximab Gemcitabine 100... Oxaliplatin 100...	16 Years -	University Hospital Southampton NHS Foundation Trust

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