Exploring the Design of the ECOG-ACRIN E1411 Trial in MCL

Mitchell Smith, MD, PhD, chief medical officer of the Follicular Lymphoma Foundation in Washington, DC, discusses the ECOG-ACRIN E1411 trial (NCT01415752) among patients with previously untreated mantle cell lymphoma (MCL).

The randomized, multi-arm, phase 2 trial evaluated bendamustine (Bendeka) and rituximab (Rituxan) induction followed by consolidation with rituximab plus lenalidomide (Revlimid) was evaluated in older patients with MCL. Patients had histologically confirmed untreated MCL, at least 1 measurable disease, an ECOG performance status of 0-2, no prior treatment for their MCL, adequate organ function based on normal kidney, liver, and bone marrow function, and more, according to Smith.

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0:10 | ECOG ACRIN is one of the United States [US] cooperative oncology groups. There are 3 main ones. In addition to that, there's something called the Alliance for Clinical Trials in Oncology and something called Southwest Oncology Group. This study used all 3 of those plus the NCI Canada cooperative group. So, it was a multi-institutional, multi-cooperative group study across all the US and Canada.

0:34 | This [phase 2] study was conceived in 2011, so a little more than 10 years ago, and at that time, the initial treatment of mantle cell lymphoma, it's still a bit unclear, but at that time, using a drug called bendamustine along with a monoclonal antibody, rituximab, was common. We call that BR. What is still a bit unclear, even now, was then whether rituximab given additionally as a consolidation of maintenance treatment would be beneficial. We assumed that it would be, and we wanted to see if we could improve on that, so we designed a study that had that as a base, bendamustine plus rituximab for 6 months standard treatment and for induction, and then 2 years of rituximab maintenance or consolidation. Then we asked the question, could we improve on the induction by adding a drug called bortezomib [Velcade], which was known to be active in mantle cell lymphoma and approved for use at that time? Then we asked, could we improve the consolidation by adding a drug called lenalidomide to rituximab, and then there was a fourth arm where they both got the extra drug in induction and in consolidation.

1:49 | It is a 4-arm study where everyone gets the same base and then 1 group gets bortezomib in induction, 1 gets lenalidomide in consolidation, and 1 gets both. The idea was, could we improve the progression-free survival by 1 or more of those?