IELSG 37

Title

A randomized, open-label, multicentre, two-arm phase III comparative study assessing the role of mediastinal radiotherapy after Rituximab containing chemotherapy regimens to patients with newly diagnosed Primary Mediastinal Large B-Cell Lymphoma (PMLBCL)

Description

This is a randomised trial designed to see whether observation is comparable to radiotherapy treatment after chemotherapy+rituximab for Primary Mediastinal B-Cell Lymphoma in relation to progression and long term safety. Patients will receive a PET scan pre & post R-chemotherapy.
Those who are PET negative will be randomised to receive RT or observation.

Objectives

To evaluate the possibility to spare the radiotherapy in PMBCL patients, who have become ‘PET-negative’ after a combined R-chemotherapy.

Primary Endpoint:

• Progression free survival (PFS) at 30 months from the randomization

Secondary Endpoints:

• Overall survival (OS) at 5 years from registration
• To define long term toxicities in this patient population

Trial Design

This will be a prospective randomized non-inferiority phase III trial. Patients will be enrolled on the basis of the clinical and local pathologic characteristics of their lymphoma and where possible registered before they start the chemotherapy program after achievement of their signed consent. Where treatment is required urgently, patients may still be registered to the trial up to 4 weeks after commencing cycle 1. Central pathology review will be carried out on a national basis. Storage of fresh/frozen biopsy or of the histological paraffin-embedded material will be made wherever possible. Patients will receive one of the standard R-chemotherapy regimens currently in use for DLBCL (e.g., CHOP14/21, DA-EPOCH, Mega-CHOP, ACVBP, VACOP-B or MACOP-B). At least 6 courses of Rituximab should be administered. PET/CT scans will be performed at baseline and at 5-6 weeks after the last R-chemotherapy administration. Patients who do not have a baseline PET/CT scan should have an interim scan to allow for comparison with post treatment scan. Randomization will take place after the PET/CT performed at the completion of initial R-chemotherapy. Central review of PET/CT scans will be mandatory before randomization.

All patients with a negative PET/CT scan after completion of R-chemotherapy, either with complete or partial radiological regression of the mediastinal mass, will be randomized to receive consolidation mediastinal RT (30Gy) or observation. RT should commence within 8 weeks after the last administration of R-chemotherapy
Patients with a partial response with a positive PET/CT scan will not be randomized. They will be treated according to the investigator choice (e.g., with RT or salvage chemotherapy plus ASCT with or without RT). These patients will be followed for progression, and survival analysis and response (investigator’s defined) to the chosen salvage strategy will be recorded.

Patients will continue participation in the treatment follow-up phase study for 60 months from randomization. A form will be sent to all the investigators at 10 years to collect relevant information on long term safety.

Trial Status

In follow-up

Population

This is an international trial looking to recruit at least 540 patients.

This trial is funded by the International Extranodal Lymphoma Study Group.