Clinical Trial Stopped

Some bad news last week in The Lancet Haematology: a trial that looked at the combination of Idelalisib, Lenalidomide, and Rituxan was stopped because the side effects were just too much for patients (including some with Follicular Lymphoma). It's bad news, but not horrendous news, in my opinion.

The article is called "Safety and Tolerability of Idelalisib, Lenalidomide, and Rituximab in Relapsed and Refractory Lymphoma: The Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 Trials."

Basically, they took R-squared [Lenalidomide/Revlimid] and added Idelalisib to the mix. In theory, this should work. You have three agents that attack the cancer cells in different ways. If one or two don't do the job, then maybe the third one will.

The problem, of course, is that all three agents attack the cancer in different ways, they also all have side effects. Some are only found in one of the three agents, but some come from all three. And there's the problem.

There were 11 patients in the trial -- 8 of them had Follicular Lymphoma.(That's a very small number, but this is a phase 1 trial, so that's pretty typical). Over 28 days, patients were given Lenalidomide for 21 days, Idelalisib for all 28 days, and then had a Rituxan infusion once a week. Things seemed to go pretty well until patients received the Rituxan, and then symptoms of the side effects started to show up. The researchers stopped giving Rituxan, but a few patients continued to have symptoms. They decided at that point to stop the trial completely.

Specifically, the side effects were ALT elevation (a sign that the liver was being damaged) and rash for the Mantle Cell Lymphoma patients, and neutropenia (very low white blood cell count) and rash for the FL patients. (I know I don't talk about side effects enough when I discuss research -- I'm too focused on the positive -- but it's important to point them out here because it's the whole point of the article).

The researchers say that, obviously, this combination is too toxic to use. More broadly, they say that we need to bee more careful about the kinds of combinations that we attempt in fighting lymphoma.

A couple of observations, for what they are worth, from this non-expert:

First, I think our future as patients will continue to depend on combination treatments like this one. The whole idea just makes sense -- cancer cells seem to find ways around our ways of fighting them, so we need to keep finding new ways to fight. It's kind of like keeping mice out of your house -- you find the hole that they are coming in and block it, and then when they keep coming in, you look for another hole. Keep blocking the holes until they stop coming in.

(Unless the mice were used to help create Rituxan. Then they can come in any time they want....)

The trick, obviously, is going to be to find the right combinations -- the ones that are effective and safe. Every treatment is going to have side effects. We'll need to determine whether the side effects are worth it.

Second -- I sad this was bad news, but not horrendous news. What I mean is, this combination didn't work. But the three things that make up the combination do work. All as individual agents, and in other combinations (R-squared still gets lymphoma experts very excited, and Rituxan + Idelalisib is very effective in CLL -- no word on FL yet). It's easy to be alarmed at a headline and start to get worried about different agents, but there is still a lot to be hopeful about with these three, alone, together, and combined in other ways.

The real lesson here, though, is to thank the heroes who took part in the trial. Nothing happens without trials, and trials don't happen without patients who are willing to participate in them. So here's another reminder to think about being a participant, with another link to Lymphomation.org's page on Clinical Trials -- how to find them, how they work, why you should participate, and things to think about before you do. Good stuff.

So, bottom line -- a set-back for us, but I think something good will come from it in the end.