OptiMATe

Title

Optimizing MATRix as remission induction in PCNSL: De-escalated induction treatment in newly diagnosed primary CNS lymphoma – a randomized phase III trial.

Description

OptiMATe is a randomised Phase III trial which aims to improve outcomes for people with lymphoma of the brain and spinal cord, for which current treatments are not always successful.

A previous trial (IELSG322) found that a treatment regimen called MATRix, which is a combination of chemotherapy drugs and an immunotherapy treatment called rituximab, followed by a stem cell transplant, could lead to long-term survival for around 70% of people with primary central nervous system lymphoma (PCNSL). This trial led to a change in the standard of care for this disease in the UK and much of Europe.

However, around a third of patients do not respond or relapse following this treatment, and complications are reported to be 11-28% per each cycle of MATRix (most frequently appearing in the first cycles of treatment). The OptiMATe trial will therefore investigate whether MATRix can be optimised by changes to the timings and intensity of how the different drugs are given.

Objectives

Primary:

• To demonstrate superiority of a de-escalated induction treatment strategy followed by autologous stem cell transplantation compared to the standard MATRix protocol in terms of event free survival (EFS).

Secondary:

• To compare overall survival, progression free survival, remission rate prior to consolidation and after consolidation, rate of patients reaching consolidation, complication rate, neurocognitive impairment, and quality of life between both treatment arms.

Trial Design

OptiMATe is an international, multi-centre, randomised, open label, phase 3 superiority trial, for patients newly diagnosed with PCNSL. The aim of the trial is to compare 2 different approaches to induction chemotherapy. The standard arm comprises remission induction with 4 cycles of MATRix, followed by HDT-ASCT for responding patients. The experimental arm adopts two changes aimed at optimising remission induction before proceeding to HDT-ASCT. Patients will be followed up for a minimum of 24 months from completion of treatment.

Trial Status

Open to recruitment.

Population

Immunocompetent patients aged 18-65 years (or 66-70 years with an ECOG <2) with newly diagnosed, histologically confirmed PCNSL who are considered eligible for the study treatment at the time of diagnosis.

This research is funded by the Stand Up to Cancer campaign for Cancer Research UK (award reference no. CRCPJT\100010)