INCA
Research type
Research Study
Full title
A multicentre randomised phase II clinical trial of Inotuzumab Ozogamicin plus Rituximab and CVP (IO-R-CVP) versus Gemcitabine plus Rituximab and CVP (Gem-R-CVP) for the first line treatment of patients with diffuse large B cell lymphoma who are not suitable for anthracycline containing chemotherapy
IRAS ID
106985
Contact name
Andrew McMillan
Sponsor organisation
University College London
Eudract number
2012-001900-39
Clinicaltrials.gov Identifier
Research summary
Research Summary:
The aim is to determine the efficacy and safety of adding inotuzumab ozogamicin to R-CVP in the first line treatment of Diffuse Large B Cell Lymphoma in patients who are not able to receive anthracycline containing immunochemotherapy. The incidence of DLBCL is increasing and with an expanding elderly population, the incidence will continue to rise. Given that about 40% of cases of DLBCL occur in patients aged over 70 and the number of co-mobilities increases with age, research to investigate the optimal treatment of DLBCL in this group of patients is needed. R-CHOP remains the standard of care for the majority of patients with DLBCL, anthracycline use is precluded in a proportion of these patients by a high risk of developing cardiotoxicity, especially congestive cardiac failure. Currently there is no standard of care for patients who are unfit for anthracycline treatment. It has been routine to omit the doxorubicin from R-CHOP, giving R-CVP instead. However the outcome for patients treated with R-CVP is poor and attempts have been made to replace the doxorubicin with alternative agents. The trial will compare an experimental arm consisting of Inotuzumab Ozogamicin added to the standard immunochemotherapy regimen of rituximab, cyclophosphamide, vincristine and prednisolone (IO-R-CVP) with the control arm of gemcitabine added to the same combination (Gem-R-CVP).Patients will be identified, consented and treated at sites throughout the UK. All patients will receive a steroid pre-phase. Those patients who have an ECOG performance status 0-2 after steroid pre-phase will be randomised to either Gem-R-CVP or IO-R-CVP for a maximum of 6 cycles followed by 2 further doses of Rituximab. If demonstrated to be efficacious and safe to deliver, the IO-R-CVP regimen will be tested in a phase III trial to determine whether this should become the standard of care amongst patients with DLBCL not fit for anthracylines.
Summary of results:
Patients with Diffuse Large B-cell Lymphoma (DLBCL) are usually treated with chemotherapy regimens called R-CHOP or Pola-R-CHP, however, one of the drugs used is not safe for patients with heart conditions. These patients can be treated with a variety of different chemotherapy regimens including one where the cardiac toxic drug is replaced with a drug called Gemcitabine (Gem) in a regimen called Gem-R-CVP. Although this is safe, it is not as effective as R-CHOP or pola-R-CHP. The INCA study wanted to look at whether a new drug called Inotuzumab Ozogamicin (IO) was better than Gem. Adult patients with newly diagnosed DLBCL and a heart condition were randomly allocated to receive either IO-R-CVP or Gem-R-CVP with the aim of reducing the numbers who progressed (disease getting worse, or disease coming back) or died.
INCA was sponsored by University College London and run by the Cancer Research UK and UCL Cancer trials centre with funding provided by Pfizer. It was developed through the UK Lymphoma Research group; a committee including lymphoma experts and patient representatives. 123 patients were recruited from 36 hospitals in the UK between January 2014 and April 2019.
IO-R-CVP was found to be safe, with more severe toxicity seen in the patients who were given Gem-R-CVP; mostly reductions in blood counts like white blood cells, hemoglobin and neutrophils. It was also more deliverable, with patients able to receive more cycles (average 6 vs 5) and with fewer patients needing dose reductions with IO compared with Gem.
IO-R-CVP slightly increased the time until progression or death compared with Gem-R-CVP overall. However, this difference was mostly due to deaths that occurred late (>2 years after treatment) and were not obviously related to lymphoma or the treatment. The proportion of patients who did not progress or die was still much lower than we would expect with R-CHOP or Pola-R-CHP, therefore IO-R-CVP did not show enough promise to be trialed further in a larger study. This study had shown us that IO-R-CVP is a safe and effective treatment for this patient group, but better options are still needed and trials with other promising new drugs are being developed.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
12/YH/0452
Date of REC Opinion
1 Nov 2012
REC opinion
Further Information Favourable Opinion