What Patients with CLL Need to Know About Clinical Trials

By participating in clinical trials, patients with cancer have the opportunity to find themselves on the frontlines of science, as one expert explained.

“There are different trials, which are appropriate for different phases of the disease, and patients can explore [their options] based on where they are, it's always good to ask,” said Dr. Farrukh T. Awan, Professor of Internal Medicine and Director of the Lymphoid Malignancies Program at the Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center.

Talking with CURE as part of the “Speaking Out” video series, Awan explained specifically what patients with chronic lymphocytic leukemia, or CLL, need to know about clinical trials that may be available to them.

CLL and SLL ‘Are Similar Entities’

There are many clinical trials for patients with small lymphocytic lymphoma, or SLL, that will accept patients with CLL, and vice-versa, Awan noted, speaking on behalf of the Leukemia Research Foundation.

“In my mind, CLL and SLL are similar entities,” he said. “So, sometimes the clinical trials may be advertised as SLL clinical trials or CLL clinical trials, [but] most of the time, they will include both those patients. And there are minor differences between how you would diagnose SLL and CLL, but essentially, they're the same exact entity. So the clinical trials are also fairly similar for both of them.”

CLL, according to the National Cancer Institute, is a type of cancer that involves the bone marrow producing too many lymphocytes, a type of white blood cell.

The National Cancer Institute states that SLL is the same disease as CLL, but in the former cancer cells are found mostly in the lymph nodes while in the latter they are found mostly in the blood and bone marrow.

Types of Trials

There are numerous clinical trials for patients with CLL, “it just depends on where you go and who you talk to and what organization or institution you're getting your treatment at and what your geographic area is,” Awan said.

Awan explained the different types of clinical trials available to patients with CLL.

Early Intervention Clinical Trials

In early intervention trials, Awan explained, patients are treated before they would need it if following conventional criteria. These trials are especially used among patients with high-risk CLL, which he defined as a more aggressive category of disease that requires treatment right away.

“Generally, in CLL, we don't treat the patients early, because they may not need treatment for a long period of time, and early treatment has not shown to improve survival,” Awan said. “So that's why we treat patients when they need treatment, so this is why some people have argued, ‘Hey, can we at least take a group of patients with high-risk disease and treat them early? And hopefully, with early treatment, you can control the cancer faster and better. And they may have a longer, better outcome?’ And the answer is possibly.”

Frontline Trials

Many current trials are frontline trials, also known as first-line treatment trials, in which approved treatments are combined in various forms and durations in order to improve patient outcomes.

“The big debate in that is, how do you sequence treatments? Do you use two treatments together? Do you use one? Do you use three? And [for] how long? So, these are questions that are being aggressively and actively addressed in the CLL arena, and hopefully we will have an answer over the next five-ish, maybe 10-ish years [as to] which strategy is the best. Is that the on/off strategy [where] you treat for a year, let's say, you get four, five years [off] and then you treat again versus you just treat and then you keep the pill on and the patients will have a very good outcome?”

Relapse Setting Trials

The majority of trials, Awan said, occur in the relapse setting, where a patient’s cancer has returned following prior treatment.

“The biggest focus in those trials right now is working on second- or third-generation drugs which work, even if the old-fashioned — and I say old-fashioned but those drugs have only been around for 10-plus years so they're not that old — but we're starting to see that the cancer has evolved and in some patients have become resistant to treatment with these older generation of drugs,” Awan said. “So the newer generation of drugs are able to overcome some of the resistance issues that we are seeing with the first or second generation of drugs. How do we use them? How do we incorporate them into our treatment? That's being addressed.”

Phase 1 trials

Early-stage, phase 1 clinical trials represent a particularly exciting frontier for new treatments, as Awan explained.

“Phase 1 trials are the first step in trying to figure out what dose you will use and what dose would work and what dose would not be very toxic,” Awan said. “Without doing a phase 1 trial, none of your drugs would have been approved. And to give you an example, when we were treating patients on the phase 1 trial of the first-generation drugs [for CLL], we had phenomenal responses, and though not all the patients, some of them are still alive to this day. And back then those patients had failed everything that was available at that time point.

“So, the point was that people are generally reluctant and leery about participating in phase 1 studies, but I actually encourage them to consider those because sometimes that's the most exciting and early opportunity to get involved in a molecule or a compound which probably has the best activity in the lab, and in non-human primates or mice and whatever. So that's how they move it to the human studies. But sometimes you get the best benefit out of those new, exciting treatments. And we're actually very excited about a number of those currently, that are ongoing right now, because they work completely differently from what we've had in the past.”

‘You’re Not Being a Guinea Pig’

“You're not being a guinea pig if you participate in clinical trials,” Awan said. “That's not what this is about. Most of the trials in our field are asking very specific questions: How do you improve outcomes? Most of the trials that we have are already with FDA-approved treatments, so these are not new treatments, these treatments have been there for a long period of time with proven efficacy, we just want to combine them and use them in different areas so that we can improve the outcomes for our patients.”

One concern among patients regarding clinical trial participation can be the chance of receiving a placebo, defined by the National Cancer Institute as an inactive substance or intervention that looks the same and is given in the same way as the treatment that is being studied.

While trials using a placebo control group do happen, Awan said that “this is almost always in a setting where you can justify that doing nothing or a placebo may be the right answer, because you don't want the new drug to be worse than doing nothing.”

Generally, a “very small” percentage of clinical utilize placebo, Awan said.

“I think there's a lot of misconceptions, mistrust in certain communities [and among] certain people about participating in a clinical trial, but the answer is most of the time, that is the correct answer for a lot of our patients,” he said. “And it has nothing to do with you being a guinea pig or being exposed to placebo. … That's what I really feel strongly about. And that's the first thing I talk to them [about] when I'm discussing the clinical trial with my patients.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.