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What Is a Clinical Trial? MPN Experts Explain

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Published on January 11, 2018

It is well-known that researchers find new ways to improve treatments and quality of life for patients through clinical trials, but how do they work? MPN experts Dr. Srdan Verstovsek, Dr. Abdulraheem Yacoub and Dawn Urbanovsky discuss how patients can join trials, procedures for participating and MPN therapies in development. Tune in to find out more. 

Produced in partnership with The University of Texas MD Anderson Cancer Center. We thank Incyte for their support.



The University of Texas MD Anderson Cancer Center


The University of Texas MD Anderson Cancer Center

Transcript | What Is a Clinical Trial? MPN Experts Explain

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Beth Kart Probert:

There are more medicines and treatments on the horizon, which is very wonderful to hear. And I’d like to bring up the topic of clinical trials. And, Dr. Yacoub, if you could tell us what is a clinical trial? It could be a little overwhelming to understand.

Dr. Yacoub:         

Well, thank you very much. This is actually probably the most important thing we do as physicians is to advance science. And that’s how we’re able to build that list of medications is through a lot of hard work and a lot of clinical trials with a lot of patients volunteering their time and effort to enroll in clinical trials to get those medications approved and available for the rest of us. So this is how the science advanced to this point. And I think it’s everybody’s obligation to keep that momentum going.

A clinical trial is designed to answer a question. There’s knowledge that is lacking. There’s a question that doesn’t have an answer. So we design a clinical trial to answer the question. The question could be defined what is the normal. So there are trials that are not for treatment. They’re just to collect information. It’s registry style trials. And we’re going to talk about some of them today. But that is a question. We do want to define what is the status quo, what is the need, what are the unmet needs that need to be addressed?

In addition, there are interventional trials, or treatment trials, which introduce a new molecule or a new drug that has promise that has passed some safety inspections and safety phases and is expected to help patients with certain diseases.

So the trial will be designed to test if that medicine is effective. Sometimes, the trial is randomized, and you might be getting the promising drug. And sometimes, you might get the control or a placebo. So there is that unknown trial for the patient and for the physician. But it’s unavoidable inevitable need that we have to perform these studies to know if the new studies that are actually effective and safe. We’ve had trials where we investigated drugs, and they turn out to be not effective. We’ve had occasions when we investigated drugs, and they turn out to be unsafe. 

So without running the trial, we would not know that information. So that’s why a lot of the design is very solid and regimented. And we all adhere to it in order to advance science.

And that’s how we got to the point we’re in today. And we hope to keep advancing this momentum to advance more clinical trials. The clinical trial identification starts with the patient looking at our website or the patient talking to their physician or the physician approaching the patients. There is more than one way this could be approached. And I’m sure we have a wonderful team here today who have excellent experience in doing this. And once the patient identifies the trial that will be appropriate for him, it could be national where they have to travel for it, it could be local, it could be online.

There are different forms of communicating. And once the patient identifies a trial that they’re interested in, there’s a lot of education that goes on from there and a lot of subsequent steps that happen. And, hopefully,it ends up with good results.

And that’s really going to advance the field, whether it’s for that individual patient or for future patients who will benefit from the results of that research. 

Beth Kart Probert:

And you brought up a burning question I always have, and I’m going to direct this to Dawn, because I’m guessing you hear this quite often. Dr. Yacoub, saying that, sometimes, the patient gets a placebo, and, sometimes, they get the medication. Dawn, I wanted to ask you do you have patients who are on the fence and not willing or wanting to do this or maybe don’t have a full understanding of that particular part of being in a trial? And how do you discuss this with them?

Dawn Urbanovsky:           

That’s a very good question. We do have many patients participating in trials. Some are usually very anxious to be involved in a trial, and others are a little bit reluctant. So I think it’s important to coordinate them being able to meet with our research staff.

We have research nurses and study coordinators that are very knowledgeable about the particular clinical trials that they’re involved with, as well as the information. And that coordinated with the conversation with the physician kind of helps that patient determine what’s going to be the best decision for them and give them the answers that they need to decide whether or not to participate.

Beth Kart Probert:           

Dr. V, I’d like to ask you, so, we’ve got clinical trials going on. How do medicines get approved, at this point?

Dr. Verstovsek: 

This is a good extension of what we have talked so far, because there are other stages of drug development and different types of studies. Placebo control studies so where the patient is randomized between the two arms getting medication or not getting any therapy at all are very rare.

And these are usually needed only in the case where the drug is at the level where there is a high probability of being successful, and it’s for approval. This is to say that the Stage 1, 2 and 3 exist in a drug development. Stage 1, or clinical trial where it’s a clinical trial where we test the safety first. So, there are those escalations from very low dose that would probably not cause much of any harm and perhaps not even efficacy. But it’s necessary to establish the baseline. Patients, perhaps three patients, are treated to that dose.                 

If it’s safe, you go to higher dose with another three patients and follow the same pattern until you establish the safety and possible efficacy. That’s Phase I. Those escalation Phase I safety study. The second is the Part 2, or Stage 2 is where you define the dose, and now treat many more patients, 50, 100 patients, a certain number with the same dose and same schedule trying to define the real efficacy of the drug with the same dose.

And only then you go to more advanced studies, Phase III, where you will do a randomization. And not only that, you may have studies where you randomize patients within the drug and placebo, there are randomized studies, and we go there more and more, where you randomize patients between different therapies. Perhaps established therapy where it is a new therapy. We call this best available therapy, one arm, and investigation agent the other arm. These are, obviously, much more in favor both from the patient’s perspective and from the physician’s perspective not to treat patients with placebo but to treat patients with standard care where it is a new, possibly more effective therapy.

So, three stages, 1, 2, 3, to get the drug to approval. But what we have also talked about it, and Dr. Yacoub brought his up right from the get-go, is that we are moving from international studies, which are essential for new drug development, no question about it, to understand the problem much more broadly through the life of the patients that have good life expectancy like patients with ET or patients with PV.

To understand what the lives bring to them, these are observational studies. Trying to understand what are the real problems in the life of the patient and not to wait only for a blood clot to develop or progression to myelofibrosis to happen, and then, to intervene—but to find the ways to identify problems properly and perhaps intervene earlier, if not to intervene right at the diagnosis. But at least to have a better view and understanding of life with the disease and identify patients that may need therapy sooner rather than later. 

Beth Kart Probert:           

So we’re talking about clinical trials. And I know that both of you probably have some clinical trials that you’re both excited about. And, Dr. Yacoub, if we could start with you, we’d love to hear about them.

Dr. Yacoub:         

Thank you so much. Again, this is a topic I’m passionate about. So please excuse me if I get very passionate about it.

Beth Kart Probert:           

We love it.

Dr. Yacoub:         

So, clinical trials, just like Dr. Verstovsek explained, go into multiple phases. So Phase I and Phase II are meant to evaluate if the drug is safe all together or has any activity or a confirmed activity. And then, more advanced clinical trials have more randomization to try to establish a new standard of care. A very good example is the COMFORT clinical trial that Dr. Verstovsek led nationally or internationally and resulted in approval for ruxolitinib and Jakafi for the patients with myelofibrosis. So that was a landmark study, and that’s a perfect example of a successful clinical trial.

And that has been the biggest progress in myelofibrosis maybe through its history. Since then, we’ve used the drug very effectively.

And it’s been a godsend to many patients—but not to every single patient and has not cured a lot of anybody. It’s not a curative therapy. So there is a medical need. There is need to improve on what we have right now. And what we have right now is much better than we had back then because of those clinical trials. So, one trial, for example, is a trial for patients on ruxolitinib who are doing well but could do better by adding another molecule to it. So combination trials are becoming more common. And there are multiple combinations, but there are also some of them have been done and completed and presented.

Some of them, actually, are very effective. Some of them are still under investigation. So that’s one path of clinical trials that we’re trying to explore, at this time. It’s combination with ruxolitinib in patients already ruxolitinib and doing okay or doing well or could be better.

And then, the ruxolitinib is, again, a very effective therapy for most of the patients. Some patients are not eligible for it. Or some patients receive it, they benefit from it for as long as it does benefit them, and then it quits benefiting them for different reasons. Oftentimes, it’s the cancer just changing, cancer getting resistance to the therapy. So what is next? So, we have also a wave of clinical trials that try to address that. So there have been multiple JAK2 inhibitors beyond ruxolitinib that had been investigated. Many of them have not made it to an FDA approval. Many of themmade it to a Phase III trial, so, they passed through the multiple phases.

And they got to the real test, which is the Phase III study, which investigations found this drug is actually as good as what you do as a standard of care. And, unfortunately, many of them failed to actually improve on what standard of care. The most recent of those is momelotinib, which is a drug we had a lot of promise for. It’s a second-generation JAK2 inhibitor that actually improves the hemoglobin. However, the drug was not inferior to the standard of care but not in all categories. So it is not going to, at least for now, become a viable option for our patients, which is unfortunate. 

And then, there is another JAK2 inhibitor drug that also has gone through Phase III trials. It was on clinical hold for a while, but now it’s back in clinical trials. It’s called pacritinib. So pacritinib is now in a randomized Phase II study. But there’s no placebo. So easy. It’s just different doses of the same medicine or different schedules of the same medicine. And this trial is particularly for patients with myelofibrosis who have low platelets, whether they had been exposed to ruxolitinib before or not. And it allows a different niche for this drug for patients who would need it. So, that, again, were some of the other alternatives, because there is a clinical need for those patients. There are multiple novel drugs in different phases of development for myelofibrosis as well. For ET and polycythemia vera, interferon trials are ongoing.

There will be many of them presented in this coming ASH.

And there has been some that have been conducted and presented in Europe. And they’re being conducted in the U.S. We’re using different interferons. So interferon is a very old medicine. But the newer formulation is the pegylatedone. It’s long acting and has a lot more side effects. And peginterferon alfa-2a (Pegasys) is one of those brands, but there’s others. And they’re a lot more tolerable than the old interferons. So, now, we’re able to conduct more advanced clinical trials with those drugs. And, hopefully, we’ll hear more and more about these. And they are showing up on our guidelines. 

Ao now that we have American guidelines, in addition to the European guidelines, they’re actually listed as a first-line option for our patients. And that’s not based on one trial. It’s based on the accumulation of evidence of the use of those drugs in our patients. You all heard about immune therapies. 

And that is also coming on to our diseases. So there would be also trials with immune therapy and checkpoint inhibitors for our diseases, too. 

Beth Kart Probert:           

Excellent. A lot of information. Dr. V, would you like to add to that?

Dr. Verstovsek: 

The efforts are in place at multiple centers around United States and Europe much, much more than in the past. And this is a reflection of our understanding of the biology and biological complexity of these conditions where we can, and this is the evidence on this list, identify the problems and target them with specific medications much, much better. And, therefore, combination studies where we combine medications are ongoing much more often these days than, let’s say, 10 years ago.

We understand the complexity of the disease where you need to combine medications to target multiple factors at the same timed. On the face value of it, there are many of them that are being tested. 

But, unfortunately, many of them do not make it. And even in the case of momelotinib or pacritinib, the Phase III studies, that means that under my studies to compare it to best valuable therapy, as we discussed before, did not show satisfactorily for the regulatory bodies to approve those medications. And Pacritinib is being tested in additional studies, too. Perhaps catch up and develop it, proof of real activity for approval. This is not to say that we don’t have enough novelties here to go further much faster. Immunomodulators, this is the one that Dr. Yacoub mentioned. 

This is a hot topic in oncology and hematology. Allowing immune system of the patient to recognize and fight the cancer better. ET, PV, these are neoplasms.

That means abnormal growth, benign ET, very aggressive myelofibrosis, and PV kind of in between, benign, if you like. But this is not normal. And it happened, in part, because immune system allowed it to happen. We all have immune system surveillance in our body that would eliminate arising abnormalities. And, in patients, that did not work very well. And, if you can boost immune system by allowing the immune system cells to recognize malignancy and kill them, then, you can help patients. 

And that has been proven in many patients with solid tumors, lung cancer, lymphoma, GU cancer, GI, many other conditions where we already have approved medications, immune modulators, for these conditions. These same types of medications are being tested in myeloproliferative neoplasms. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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