P+R-ICE

Title

An open-label, multicentre, randomised phase II Pembrolizumab in combination with R-ICE chemotherapy in relapsed/refractory diffuse large B-cell lymphoma.

Description

The study has two treatment arms to which participants will be randomised on a 3:1 basis to the experimental arm.

The control arm (Arm A) will be R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan). The experimental arm (Arm B) will consist of P+R-ICE for 3 cycles followed by an autologous stem cell transplant (for patients in a CR or PR on the post treatment PET-CT scan) and maintenance Pembrolizumab every 3 weeks for one year. All patients will be randomised at study entry and will be stratified by relapse within 12 months or > 12 months of first line therapy.

• UK Sites – 9
• Recruitment target – 65
• Recruitment period – 24 months

Objectives

Primary:

• To establish the event-free survival at 1 year in patients treated with P+R-ICE.

An event is defined as any of the following:

• Progression  / relapse of lymphoma
• Stable disease at 3 cycles of therapy
• Commencement of any unplanned non-protocol treatment for lymphoma
• Death from any cause

Secondary:

• To examine the longer-term (2 year) efficacy of P+R-ICE
• To assess whether the addition of pembrolizumab has an impact on the ability to harvest sufficient peripheral blood progenitor cells for autologous stem cell transplant
• To assess the number of patients achieving CR following treatment with P+R-ICE
• To document the safety and toxicity profile of P+R-ICE
• To document the anti-tumour activity of P+R-ICE in patients with relapsed or refractory DLBCL

Tertiary:

• To correlate clinical outcomes with gene expression analysis of PD-1, PD-L1, PD-L2 and other immune signatures from primary tumour material.
• To correlate clinical outcomes with immunohistochemical expression in tumour material of PD-1, PD-L1, PD-L2 and other markers in both tumour and microenvironment
• To correlate clinical outcomes with expression of PD-1, PD-L1/L2 on peripheral blood T-cells. Subdivision of T-lymphocyte sub-sets

Trial Design

Trial Status

Open to recruitment.

Population

Population over 18 years old with relapsed/refractory diffuse large B-cell lymphoma.

Funder

This trial is funded by Merck Sharp & Dohme (MSD) known as Merck & Co.

Any additional costs will be covered by SCTU.