ARGO
Research type
Research Study
Full 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.
IRAS ID
205320
Contact name
Andrew Davies
Contact email
Sponsor organisation
Southampton University Hospital
Eudract number
2016-002654-21
Duration of Study in the UK
5 years, 10 months, 29 days
Research summary
Research Summary
Diffuse large B-Cell lymphoma is the most common subtype of non-hodgkins lymphoma, accounting for around 40% of the diagnoses. Current treatment uses a combination immunochemotherapy resulting in a cure in around 60-70% of patients who are treated within a clinical trial setting. It is recognised however that the outcomes found in clinical trials are generally better than those in the general population, which in this condition, although increases have been seen, has survival rates just under 60%. This difference is possibly due to the under-representation of the elderly in clinical trials who generally have poorer outcomes due to numerous comorbidities and the effects of chemotherapy toxicity on their health.
Second-line strategies for such patients only provide an event free survival rate of 20% at 3 years, however this is only in those who are fit enough to receive the high dose therapy and who relapse within 12 months of primary treatment. For those patients who aren’t able to have these treatments the outcome is quite poor (survival less than 6 months). It has proven challenging to find effective treatment strategies for this group. As the incidence of DLBCL is rising and around 40% occur in those over 70, it is necessary that an effective treatment be found.
Recent studies using a combination of rituximab, with oxaliplatin and gemcitabine (GemOx) in this population achieved a 44% complete response rate after 4 cycles of treatment and a 5 year progression free survival rate of 13%. This study intends to build on this success by using the R-GemOx in combination with a new antibody, atezolizumab in the hope that this will improve outcomes. Participants will be randomised on a 3:1 ratio to receive the R-GemOx with atezolizumab in comparison to R-GemOx only.Summary of Results
This was a phase 2 trial conducted in the UK only. The trial was sponsored by University Hospital Southampton NHS Trust, funded by F.Hoffman-La Roche and coordinated by the Southampton Clinical Trials Unit.
PURPOSE
This trial looked at whether the drug, atezolizumab could improve treatment for people with non-Hodgkin lymphoma called Diffuse Large B-cell lymphoma (DLBCL).
Atezolizumab aims to trigger the immune system to attack and kill lymphoma cells. The study looked at whether adding Atezolizumab to standard chemotherapy which included rituximab, gemcitabine and oxaliplatin (called R-GemOx) would improve the way it worked.
PARTICIPANTS
The trial involved people whose lymphoma had come back (relapsed) or continued to grow following at least 1 or 2 different types of treatment (refractory). Between July 2018 and March 2020, a total of 53 patients with DLBCL were enrolled onto the ARGO trial across 14 hospital sites in the UK.
Following national guidelines, recruitment to the ARGO trial was temporarily stopped in March 2020 in response to the COVID-19 pandemic. Participants who were receiving treatment continued to do so and the number of hospital visits were reduced to lower the risk of getting Covid.
TREATMENT
For the first cycle of treatment, all patients received rituximab, gemcitabine and oxaliplatin therapy (R-GemOx). For the remaining cycles patients were randomly assigned, in a 1:3 ratio, to one of two arms either; Arm A, R-GemOx or Arm B, R-GemOx plus atezolizumab (R-GemOx-Atezo).
Arm A-cycle 1-6 R-GemOx
Arm B-cycle 1 R-GemOx, cycle 2-6 R-GemOX-Atezo Of the 53 patients recruited: 12 patients received R-GemOx (Arm A) and 41 patients received R-GemOx-Atezo (Arm B).
After 6 cycles of treatment, all patients had an imaging scan (PET-CT) to assess their disease. Those patients in Arm B whose scan showed that their disease had remained stable or improved, continued to receive a further 8 cycles of atezolizumab only. All other patients were followed up regularly for observation.
A number of blood samples were taken from each patient at various timepoints during the study.
SAFETY AND SIDE-EFFECTS
Although all patients experienced an adverse event (side effect), overall, the combination of R-GemOx-Atezolizumab was found to be safe, since the main adverse events reported were similar to those seen in patients treated with R-GemOx.
RESULTS
In June 2020, analysis of the study data collected so far (53 patients) did not show a significant benefit when atezolizumab was added to R-GemOx. Even if the study had continued and recruited the total number of participants planned (112 patients), it would not have shown a difference. Due to the COVID-19 pandemic it was felt that it would not be right to ask the participants to continue to attend hospital for a treatment that was not showing benefit, when the risk of getting COVID-19 was high. Therefore, treatment was stopped and all participants were asked to move to the follow-up phase of the study. Initially, the follow-up phase of the study was designed to last for 36 months (from the start of treatment), but it was agreed that the follow-up phase would be stopped early as it was of no benefit to patients or the scientists. Therefore, follow up ended for all patients in January 2021.
CONCLUSION
The conclusion of this trial is that the addition of atezolizumab to R-GemOx did not improve its effectiveness in treating patients with refractory or relapsed disuse large B cell lymphoma.
As an additional finding, exploratory analysis of patients DNA samples may point to a biological subtype of patients that may benefit from the addition of atezolizumab.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
17/SC/0533
Date of REC Opinion
23 Nov 2017
REC opinion
Further Information Favourable Opinion