Title

Polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) versus R-ICE alone in second line treatment of diffuse large B-cell lymphoma (DLBCL).

Description

An open-label, prospective Phase III clinical study to compare polatuzumab vedotin plus rituximab, ifosfamide, carboplatin and etoposide (Pola-R-ICE) with rituximab, ifosfamide, carboplatin and etoposide (R-ICE) alone as salvage therapy in patients with primary refractory or relapsed diffuse large B-cell lymphoma (DLBCL).

The study will investigate the addition of polatuzumab vedotin (Pola) to rituximab, ifosfamide, carboplatin and etoposide (RICE), a standard chemotherapy treatment regimen versus treatment with RICE alone, in patients with primary refractory or relapsed diffuse large B-cell lymphoma (DLBCL).

Over 50% of DLBCL patients will not achieve a remission with standard second line salvage therapies. Therefore, there is an unmet medical need to optimise second line therapy in progressive and relapsed aggressive B cell non-Hodgkin lymphoma.

Polatuzumab vedotin is an antibody drug conjugate, targeted to the CD79b antibody expressed on a majority if B cell derived malignancies. In initial studies, polatuzumab vedotin has shown very promising response rates. The RICE regimen will be used as the comparator/standard arm. RICE is regarded as less toxic than some other regimens but still with comparable response rates.

This is the first study to assess the Pola-RICE combination and as such, as well as efficacy objectives, particular attention will be paid to safety objectives.

Objectives

Primary:

• The primary objective of this study is to investigate the following question in patients with relapsed or primary refractory DLBCL: Does salvage therapy with Pola-R-ICE improve event-free survival (EFS) compared to R-ICE alone?

Secondary:

The secondary efficacy objectives of the study are to collect data in order to evaluate whether the addition of polatuzumab vedotin to standard therapy R-ICE:

• Enhances the rate of metabolic complete response (CR) at the end of study treatment.
• Enhances the partial response (PR) rate and overall response rate (ORR) and decreases the progression rate and relapse rate.
• Enhances the duration of response, progression-free survival (PFS) and overall survival (OS).
• Impacts the mobilization of autologous CD34+ stem cells.
• Enhances the rate of patients proceeding to transplantation.
• Impacts the non-relapse mortality.

Further secondary objectives of the study regarding safety, protocol adherence, quality of life (QoL) and biology are to collect data in order to evaluate; adverse and serious adverse events, incidence and duration of neutropenia and thrombocytopenia Grade 4 CTC, rate of treatment-related deaths, number of second malignancies, cumulative and relative doses, and QoL, as well as to provide samples for translational research.

Trial Design

This is a multicentre, international, open-label, randomised phase III trial.

The study will have two treatment arms; Pola-RICE vs RICE and patients will be randomised on a 1:1 basis.

The study will aim to recruit 334 patients across 4 countries; Germany, Austria, Spain and the UK. 75 patients will be recruited from the UK.

Following informed consent, all patients will receive 3 cycles of chemotherapy; half the patients will receive Pola-RICE and half the patients will receive RICE.  Patients will then be followed up (3 monthly visits) for at least a further 21 months. Therefore, each patient will be involved in the study for a minimum of 24 months.

Trial Status

Closed to recruitment. In follow-up.

Population

Patients aged 16 years and over with relapsed or primary refractory DLBCL.

 

The study is an investigator-initiated trial with financial support by F. Hoffmann-La Roche Ltd. The trial is endorsed by Cancer Research UK (award ref CRCET\100004) and NIHR adopted.