Clinical Trials for Leukemia and MDS

Clinical Trials for Leukemia and MDS -  5.12.26 Transcript

Participants:

Dr. Uma Borate, The Ohio State University, The James Cancer Center

Lindsey Whyte, Leukemia Research Foundation

 

- So welcome everyone. Thank you so much for joining us, and sorry again for the slight delay, but this is the second webinar in our Spring Series. Today's focus is on Clinical Trials for Leukemia and MDS. We're joined today by Dr. Uma Borate from The Ohio State University in Columbus, Ohio, who will talk through some important aspects of clinical trials, definitions of terms used, and types of trials, and how to talk to your care team about trials. She will also respond to questions from participants. My name is Lindsey Whyte and I am the Director of Programs and Partnerships at the Leukemia Research Foundation, and I'm so glad that you're all here.

 

I would like to take a moment to thank the presenting sponsor, supporter of this series, Johnson & Johnson. Additionally, our sustaining supporters are AstraZeneca, Jazz Pharmaceuticals, Merck and Syndax. Finally, the supporters of this clinical trial session are Astellas, Rigel and Menarini Stemline.

 

The Leukemia Research Foundation's mission is to cure leukemia through innovative research funding and to support patients and families. The Foundation has raised over $95 million in support of its mission since our founding in 1946, and has funded research grants to over 750 investigators worldwide. Our support programs for leukemia patients and their loved ones include information and resources on our website, education programs, and a directory of other helpful organizations.

 

For today's program, all participants will be muted, but we welcome your questions in the Q&A box at the bottom of your zoom screen. Please note that you should check the box that says anonymous if you prefer for your question to be anonymous. Otherwise, your name may show. If you already submitted a question at registration, please know that we have your questions and we will do our best to cover as many as possible. Also, we have noted that there are several. Sometimes there are note takers, virtual or AI note takers, and sometimes that can be problematic. So if we see some virtual note takers, we may ask them or remove them from the webinar.

 

After today's program, you will be sent a brief evaluation through email. Please take a moment to complete the questions and the evaluation so that we can improve future programs. Also, this webinar will be recorded and a link to it will be sent to all registrants for anyone who needs to leave early or if you would like to watch the replay with captioning or a transcript on your own time. And as I said, the AI scribes and automated note taking tools will potentially be removed from this session. So now, on to the important part of today's session. I'm going to briefly introduce Dr. Borate and then we'll move on with the program.

 

So we're grateful today to have Dr. Uma Borate with us to cover this important area of clinical research in the development of new and effective treatments for leukemia and MDS patients. Dr. Borate is a hematologist specializing in the treatment of myelodysplastic syndromes, acute myeloid leukemia, myeloproliferative neoplasms, and clonal cytopenias of unknown significance. She received her master of science in pathobiology and molecular medicine from the University of Cincinnati and completed a fellowship in hematology oncology at the University of Alabama. Her clinical and translational research focuses on novel therapeutics in myeloid diseases, particularly in disease progression from cytopenia and early stage MDS to AML. Dr. Borate is the principal investigator for numerous investigator initiated trials based on laboratory science, including a promising study exploring novel combination of targeted therapies for myeloid malignancies. She's also the national, which she might talk about today, she's also the national lead and site investigator for several early phase and industry supported MDS and AML studies, and she addresses both upfront and relapse refractory disease. Her work has been published in several peer reviewed journals, and she's also serving as a professor of internal medicine at the Ohio State University. Dr. Borate's dedication to advancing treatments for myeloid malignancies through clinical trials and translational research underscores her commitment to improving patient outcomes and contributing to the goal of cancer-free future. Thank you so much for joining us today, Dr. Borate. Thank you. And please, let's get things started.

 

- Thank you, Lindsey, for the kind introduction. I just wanted to make sure you guys can see my slides.

 

- Yes.

 

- Okay, great.

 

- It's, yep, there we go. Perfect.

 

- So I'll start by, you know, one thanking all of you for joining. I know many of you have probably dealt with a diagnosis of all the various diseases that Lindsey just mentioned and many others like other types of leukemia like CLL and, and there's, you know, unfortunately a lot of different blood cancers that afflict people. So I'm hoping that in my talk I can give you a broad overview of the different types and phases of clinical trials there are. Understanding how we study cancer therapies and maybe that will help you in your therapeutic journey to try figure out, you know, what makes sense for you when you talk to your treating team. So I'll just start by a very basic definition of what a clinical trial is and the, you know, simple sort of definition is it's a research study and it involves human volunteers and we'll talk about, you know, what that means. But I think the key thing for anybody who is a patient and is interested in participating in a clinical trial, I think all of you should know it is voluntary. When you are signing a consent form that says “yes, I will participate” of course there are, you know, schedules and expectations, but it is still a voluntary act. It is not something that you necessarily, you know, are, you're not signing in a contract that you can't at any point say, well, I no longer wish to do this. It is totally voluntary or should be totally voluntary. And we do clinical trials for multiple reasons and we'll go over kind of the different phases and what each trial accomplishes. But really what we are trying to get to is help answer questions about safety, effectiveness, sometimes even prevention, sometimes early detection, and really the management of a variety of diseases. Obviously for today's talk we're going to really focus on cancer and blood cancers, but this is broadly applicable really to any disease.

 

So why do they matter? Why are we even talking about them? Why are all of you joining this webinar? Because the reality is for a lot of people who are diagnosed with cancer, blood cancer specifically, but you know, many, many cancers, we want better treatments. We're not satisfied with what we have right now. Of course, some cancers, we have really good therapies and high cure rates, but that's not the norm. And we want to do better. We also want to improve the safety of our treatments. So if a treatment is very effective, but you have to go through a lot of suffering to endure that treatment, I think as a patient, people go through a lot, but they shouldn't have to. And so if we can deliver something more safely, we would really, really like to understand that. We'll talk a little bit about preventing disease. So these are a very different type of trial. This is even before you develop disease. We would obviously love to find cancer early if it makes sense to try to treat it early. And then lastly, there are trials that really are looking exclusively at quality of life and trials that really try to gather evidence to support other interventions that don't need, you know large clinical trial with a lot of participants, but really look at information that's already out there.

 

So this is sort of the landscape of the main type of clinical trials, like I talked about. You have treatment trials where when you are in the trial you are undergoing some sort of treatment and a specific type of treatment or treatments are being studied. You have prevention trials where maybe you're at a high risk for a certain cancer or a certain disease and you are taking a treatment that aims to prevent that cancer from ever occurring. There are trials called screening trials where you're really trying to understand different aspects of, you know, how patients kind of develop certain things. Diagnostic trials so we are trying to study a diagnostic modality to see how well it picks up a certain disease.

 

There's been a lot of interest in looking at different types of ways to detect cancer early. Some of it, you know, we have our traditional imaging techniques, but there's now a lot of new technology. And so that's being studied really with a lot of interest. There's trials, like I said, that focus on quality of life to answer very specific questions about how patients feel while going through certain therapies. And then there are some trials where you're not really doing a specific intervention, you're really observing throughout the course of a disease kind of journey. What is going on? Of course, this may involve getting treatments as well, but it may also involve a time when people are just being closely watched to see if the disease is getting worse or not.

 

So trials can come in many, many different flavors and we'll go into details of some of the ones that might be most relevant to you. So I wanted to touch a little bit on prevention trials because I think this is an area of a lot of interest for people with cancer because once you've been diagnosed with cancer and once you've sort of understood what it means for you, you might want to potentially find ways to prevent it maybe in your family members, maybe in your children.

 

And so there's many different trials that could involve vaccines, different supplements. I know this is something that people are very interested in. Different medications that, if given early, could maybe prevent some cancers from actually spreading or, or sometimes even kind of taking hold. And then obviously there's a huge interest in lifestyle changes too, because we're all very interested if there is something that we're high risk for and we can do something to control it, we would want to. And so vaccine studies are a great example. You don't have the disease yet. Maybe there's a way to target the cell that could become cancerous by doing cancer vaccines the same way you do it for your, you know, polio vaccine or other vaccines. So you don't end up getting polio or you don't end up getting shingles. Can we do that for certain cancers?

 

The other trials, as I mentioned, they're sort of early detection trials. These can be called screening trials or diagnostic trials where you are looking at different modalities where you are trying to pick up the cancer early. So the ones that we are all most familiar with, these are not trials. These are things that our primary care doctor can order for us. When you reach a certain age, doing frequent colonoscopies to detect colon cancer early by looking at polyps, doing mammograms to detect breast cancer early, sometimes, you know, high risk people can get their PSAs checked to detect prostate cancer early. These are all examples of screening or diagnostic trials. And like it says on the screen, you can do this with imaging studies sometimes as blood tests, there's a lot of interest in blood tests that can maybe, you know, do certain genetic tests that can tell you if a cancer is present in your body even before anybody might know it.

 

And then there's genetic testing. If you have a family member that's been diagnosed with a high-risk cancer, there's definitely ability to screen certain family members for that high risk gene mutation as well. The most common one is BRCA1 and BRCA2, which makes people at high risk for breast cancer, uterine cancer, ovarian cancer, but also for men. BRCA2 makes them high risk for prostate cancer. So there's definitely examples of genetic testing for high-risk cancers that is out there.

 

And then last but not the least, I definitely want to emphasize that if there are quality of life studies or observational studies where you're looking at a cohort of people, so a large group of people, they're living their lives and they have said, you know what, I will come in every few months, every few years to give you my blood to tell you about my lifestyle. And there's many, many examples of these type of studies that have given us invaluable information. There's a nurses health study where a large group of nurses participated for years and years and years and they were just followed. They were followed for how they lived, they were followed for what outcomes they had, whether it be cardiac disease, cancer. So all these studies really help us understand what lifestyle measures, populations, or people can take to help their overall health. And in terms of cancer, this is very, you know, of interest to a lot of us because we know cancer therapies affect people's quality of life, right? We know they affect everything from sleep to neuropathy to fatigue to pain. And so these are very, very important probably I would say sometimes as important as finding new and exciting drugs for people.

 

So let's talk about what we're really, a lot of us are really interested in. We're really interested in treatment trials, right? Because many of us on this webinar and the people that I've seen in my clinic anyways, have been diagnosed with some sort of blood cancer. And they always want to know, are there trials that they should participate in that might improve their chances of living longer, of maybe being cured, of a better quality of life? And these trials can study everything. They can study cancer medicines, but they can also study different surgeries, they can study different types of radiation, maybe there's a device that can help with certain types of cancer treatments. And then they can also study lifestyle treatments. So for example, we have studies where people are assigned a certain diet or people are assigned a certain exercise program along with the treatments they're taking to see if that helps, you know, everything.

 

So, but the most common one, as many of you know, is testing whether a new cancer drug works better than the standard treatment that is already out there. So this is something that I get a lot of questions on. Patients are worried, confused, curious, and sometimes this really determines if they are interested or not interested in sometimes participating in a trial. So clinical trials, if they're looking at a new cancer drug, are typically divided into different phases. The first phase of the trial is a phase one trial. And the real question of phase one trial is trying to answer is, is this treatment safe? And so if you think about it, if you have somebody with an advanced cancer that has been through multiple therapies, maybe multiple clinical trials, and there is a new drug that's been maybe tested in animals and in cells and there's promise there and it now has to be tested in humans, typically a phase one trial is for people that have tried many, many different types of therapy, don't really have a lot of different treatment options left, are otherwise doing okay and want to try something that's new that maybe hasn't been tested in a lot of humans right now, that is a phase one trial. It's one of the earliest trials that is done in people with a disease. There's not a lot of information at that point about the drug's safety and effectiveness. And when I tell, when my patients participate in a phase one trial, I tell them, we don't know 1) if this drug will work, we are hopeful, but we are not sure. [2] I can't tell you in detail every single side effect you may experience. We have some information from other patients who might have done this in the, you know, in the beginning of the trial and/ or studies that have been done on animals or cells. But it really is something that has a lot of unknowns and patients, I would say, depending on kind of where they are in their treatment journey, can hear that and say, absolutely we're still going to do this. If it gives us any hope, even if it's a small chance, I want to try it. I understand, I don't know anything, everything about it, I don't know if it'll help. And a lot of patients tell me, you know what, it might not help me, but it might help somebody else. And I think that is one of the most amazing things that I've ever heard from people who are struggling with their disease that are still thinking about other people. But that is sort of the bottom line for a phase one trial.

 

A phase two trial is a trial where the drug has been through phase one testing. So we know a lot now about its safety. We have a little bit of idea about its effectiveness, right? Because we've now seen what it can do in people who've had a lot of other cancer treatments. But what we really need to see in a phase two trial is does it actually show promise to continue to be explored in that disease? So in a phase two trial, it is a larger trial. The main goal of the trial is to understand if this drug is going to show promise in a certain percentage of patients, meaning it's going to help hopefully a majority of the patients that are on the trial. And if it reaches the benchmarks of being promising or effective, then it goes into the phase three trial setting.

 

And the phase three trial setting is typically the last phase of the trial before a drug gets what we call FDA approval. And the phase three trial asks the question is this drug better than what we are currently doing for that disease at that stage of the disease? So for example, if you have a new breast cancer drug, you are going to compare it against the standard breast cancer treatment that a breast cancer patient will be getting at that stage in their disease. Whether it's a new diagnosis, whether it's somebody who's seen three different treatments. So you are going to compare a group of people that get the standard treatment that would be prescribed as opposed to a group of people that will get the new treatment that is being prescribed. And sometimes it's done by itself, but a lot of times it's done on top of the standard treatment that you get. So this is typically, you know, a large trial, it's usually international, it has a lot of people that participate in it to try to understand that very important question because at that point, if this trial is successful, this drug will be available to people provided it goes through a lot of scrutiny from the FDA to make sure that these results are actually verified and legitimate.

 

And then if that happens and the drug is available, what we call on the market, meaning you can get it prescribed from anybody no matter where you're seeing them, it's not part of a trial, there is a phase four where the drug is then observed by a lot of people as regular people with the disease are taking it. Because sometimes what we've learned is once the drug is approved and it's being used by very large numbers of people, you start seeing side effects that you never saw in the trial. And there is a mechanism by which people can report those side effects even after the trial is complete and the drug has been FDA approved, they can be reported back to the FDA to let them know that, hey, these are signals we're seeing after this drug is being used by a large number of people. This might be something you want to look into. And that has actually happened with several drugs that have been approved where they have received enough reports that they go back and take a look to see was there anything that was missed when the drug was in clinical trial. So those are the sort of four phases of trial testing.

 

And just, you know, I elaborated a lot on this, but again, just to quickly go over phase one trials, you're really focusing on the safety, you're trying to find the right dose, you're trying to understand the side effects. It's usually small trial and we are really trying to understand the best way to give this drug to patients. Like I said, again, phase two we really want to see if this is working. If it's a cancer that has what we call, you know, a lot of different places that it involves, we might look at PET scans, CT scans, and at the end of the trial it really gives us information to say, yes, this drug is promising. You really should look at it in a much larger trial and try to get it FDA approved, which is a phase three trial. This is when the drug is compared to standard treatment. Lots and lots of people are involved, lots of patients are involved. We always look here to see, you know, how long are people benefiting from this drug? How long are they living overall, what are the side effects? What is the quality of life? So these are very, very big involved trials because at that point, if the trial is successful, it will go to the FDA to hopefully be approved and given to the general population.

 

So I get a lot of questions also about randomized controlled trials because people are worried that if they're on a trial, are they going to get inferior treatment, are they going to get a placebo? Meaning no treatment? How are, you know, how are these trials managed? So randomized controlled trials are really the sort of highest bar of clinical trials because they're the most unbiased way to see if a drug is really helping people. So when you're on a randomized control trial, when you enter the trial, you get assigned either the standard treatment or you get assigned the new treatment that is being tested. Typically you or the person who you are doing the trial with the center you're doing the trial with your doctor does not have a say in who gets assigned what, that's why it's called randomized. It's a random process that's done by a computer program. When your information is put in, it spits out this person should get standard treatment or this should person should get the experimental treatment. And the reason this is so important is because we all are biased, right? If I see somebody sitting in front of me, I really, really want them to get the experimental treatment. I am going to choose and pick and so will people all over the world. And so we end up choosing and picking a group of people that we think will benefit from the treatment and we're not always really good at that. So we may end up picking a group of people that don't benefit from the treatment because we think that they would, and the drug might be unsuccessful when actually it was a very promising drug. But when it's randomly done, you are using statistics and you're taking away my bias, anybody else's bias, you're just essentially letting the process run its course.

 

Now all the people in the trial are very similar. They all have the same cancer, they have the same stage. They're generally, you know, equally balanced in terms of men and women to try to, you know, remove that bias. The age range is typically a certain age range. So this really tries to help fair comparison. So at the end, if a drug is better than the standard, we know that this is an actual result that will stand up to time. It's not something that was biased, wasn't something that was picked for, the company running the trial is not trying to stack the odds in their favor. This was truly done in a randomized scientific manner. And then this result should actually count when it's being reviewed by the FDA.

 

The last trial I wanted to talk a little bit about is an umbrella trial. So the umbrella, an umbrella trial. These are very popular because these trials test multiple treatments under a single disease type. So I'll give you the example of an umbrella trial I'm part of, it's called BeatAML, it's acute leukemia, myeloid leukemia trial. Anybody and everybody with acute myeloid leukemia comes into the trial as part of the umbrella trial. Then they're under the umbrella trial. There are multiple different other trials depending on what type of AML do they have, do they have a certain mutation, do they have a certain genetic change? And then they will get assigned to the trial that's inside the umbrella trial based on the biomarker or genetic mutation they have. And this really helps with this personalized medicine approach that we're all very excited about. But you don't have to have a separate single trial for every single genetic abnormality because that can be hundreds and thousands of trials and would not be practical. So umbrella trials are used a lot in cancer where you have one cancer diagnosis, but within that cancer diagnosis you can have different genetic mutations or biomarkers.

 

And then lastly, I talked very briefly about this, but these are conducted after treatment approval. And what we really want to understand is after the drug is out on the market, as we said, are we able to monitor long-term safety? Are they really effective in what we call the real world? Yes, they were effective in the trial because all of these patients were followed closely and they came and took their treatment. But we know real life isn't that way, right? Sometimes you have snowstorm and sometimes you, you know, have a kid that you want to, you know, take care of and you can't make it to your own treatment. And so we really want to understand, does this still, is this still able to be effective in the real world? And then, like I said, sometimes rare side effects emerge that were never caught in the clinical trial and this is a really good time to understand that.

 

So just to finish up the talk and then we can get into questions. You know, these are the typical outcomes that we get from cancer trials. We're looking to see if the cancer responds. We're looking to see if people can live for a long time without their disease progressing. Obviously we're looking to see if you live longer generally, what the quality of life is. And we really want to understand the side effect and risks of a certain treatment.

 

And sometimes, when you're part of a trial, the trial may close, but then you may end up going into a follow-up trial which still monitors you. So you're still getting phone calls, you're still being asked, Hey, we know you were on a trial, the trial ended two years ago. You know, what are you feeling like now? Do you have any side effects? You know, is your disease back? You know, how long did you do well on this trial? And so there's a lot of interest in, for example, tracking cancer survivors after they have been so-called cured, after, you know, stem cell transplant, after cell therapy, after immunotherapy. Because it's important to know, well 10 years after this therapy, are they developing, you know, heart disease or liver failure or you know, dementia. I think those are the things that people are very interested in understanding as well.

 

And then lastly, some of you may already be taking part in this. These are called registry studies or longitudinal studies. Like I said, if you have a very, very rare type of blood cancer or a rare type of cancer in general, the only way to really understand how people do in the long term is to be part of a registry study where you sign up and you say, I have this cancer. And you know, tell them your specifics and then over time you, you keep continuing to update the information about what treatments you've had, what side effects you've had. So it's really a collection of data about people like you with a very rare cancer. And over time it gives a lot of information about how people do with rare cancer. So if there's like two and three of you here, maybe there's two and three of you in one state in a different country and over, you know, this registry, maybe you get information about 50 or a hundred people with this really rare cancer.

 

So I want to end by saying cancer trials look very different. I get a lot of questions about, well my friend's, you know, son is on this trial, can I do it for my cancer? And I always tell people, cancer is very different. Blood cancers are very different. The trial somebody else may be on is very different from the trial that you may be actually appropriate for. There's so many different types and genetic differences. We're trying to personalize these trials as best as possible. Your history, your exposure, your other medical problems could be totally different from somebody participating in a different trial. And so the risks and benefits are very different depending on, you know, what your history is as one specific person compared to somebody else.

 

And then the last thing I wanted to just mention is, you know, we are now very excited about what we call biomarker driven cancer trials and these stretch across different cancer types. So if you think of a trial, our current clinical trials, most of them are focused on the disease. So CLL, AML, lymphoma, leukemia, you know, that's very specific to the disease. But a specific mutation in CLL could happen in a lung cancer, could happen in breast cancer. And so is there a way to identify the specific mutation and maybe the same mutation that happened in breast cancer the drug worked really well, we would love to use that in blood cancer. And so these are biomarker driven trials across cancer types that we're also very interested in understanding.

 

So I'll end by saying, you know, just remember phase one trials are the early phase trials that are focusing on safety. Phase two is more understanding the effectiveness. Phase three is the big trial where you compare it to the current standard of care. And then phase four is once the drug's out there on the market and what are our long-term learnings from people after they've been exposed to the drug.

 

And you know, my last kind of thought as somebody who does a lot of clinical trials when when I always, you know, when I tell patients what trials are and what you know, benefit there is, our hope and my hope is that it's ultimately going to result in better care for people with blood cancer. And by better care obviously we mean better treatments, but we also mean better quality of life. We also mean more time. But we also want that time to be meaningful and not spend all the time in the hospital.

 

So that is my final slide. Happy to take any questions. Wonderful. I'll stop sharing Lindsey.

 

- Okay, thank you so much. I think you covered a lot of different types of trials, which is super helpful. And also you gave that example of the BeatAML trial, that which is an umbrella trial, which probably some people that are participating right now are even familiar with. I think it's you know, been monumental really in many ways. And I think that one of the things that makes me happiest about it is it's really sending the message that there's this concept of precision treatment, which is really changing the way that AML is approached now.

 

So I just want to remind folks that the Q and A box at the bottom of the screen is where you can submit your questions. We have one question from an astute person who's wondering how to counter the mission of Robert Kennedy, which I recognize is a very difficult issue for patients right now to see yeah, what's going on. But yeah, voting I think is the most important thing. Then we have how do genetic variants typically vary between de novo and secondary AML?

 

- That's a great question. Secondary AML is AML, for those of you who are not familiar with the term, is AML that develops secondary to other things that have happened to a person before they develop AML. And those other things are typically exposure to cancer, chemotherapy or radiation for a different cancer. So, and then when AML emerges from that, it's called secondary AML. It's also called secondary AML if they had another blood cancer like myelodysplastic syndrome before they had AML. So the MDS kind of transitions or transforms into acute myeloid leukemia. Generally secondary AML and de novo AML, the genetic makeups overlap quite a bit, but secondary AML mutations and the genetic makeup tends to unfortunately be a type of AML that is more high-risk and less amenable to our standard therapies. It, the responses are typically not as good. They have a lot more high-risk mutations with TP53 being one of those high-risk mutations. And so we have to really be innovative in how we recommend treatments for secondary AML, the clinical trials we spoke about, there's a lot of those that, you know, there's a lot of interest in that because our standard therapies don't work as well as they would for a de novo AML.

 

I don't think I can hear you Lindsey.

 

- Thank you. Sorry about that. There's a question from someone who's actually participating from India and so this is definitely a challenge for patients that are outside of the US and, in fact, you know, there are some trials that are taking place in other countries that Americans don't have access to as well. So I think if you have any suggestions for patients that are outside the US and any observations on how you see kind of collaboration with trials because many trials are global, it's just not all of them, right?

 

- I think that's a great question and I unfortunately think many if not most trials are sort of done in Europe and, and the US. Asia, Southeast Asia for obvious reasons there's not a lot of trial activity there and my plea is to drug companies, right, when they are running these large global trials, I really, really encourage them to have as diverse a population as possible that is global because I think that truly teaches us a lot of different things about the effectiveness of drugs. I think we understand now from different ethnicities for example, a lot of work on EGFR inhibitors in non-smokers with lung cancer was done because we saw these amazing responses in South Asians. South Asian women actually who were non-smokers who had just these unbelievable prolonged responses to EGFR inhibitors and then they understood from that that the biology of these drugs was very distinctive in smokers versus non-smokers. And then that became, you know, now standard of care in lung cancer and whether your smoking status and your mutation really plays a huge role in what treatment you get for lung cancer. So I do think there's a lot to be learned by doing trials globally. Unfortunately that's not something I can directly impact, so I hope you know, you find something for your mother.

 

- Yeah, and I would say also there are organizations that are local and so, you know, if that individual wants to reach out directly to me, I can potentially point them out to some other organizations like the Max Foundation for example, that are, you know, potentially a resource for patients in other countries. So. Okay. Have there been any trials in the use of procrit in association with AML?

 

- Not that I'm aware of. I think when we are treating AML it's very hard to introduce growth factors like procrit and other ESAs primarily because we are really suppressing bone marrow function for the leukemia but also normal bone marrow function. So it would be sort of like, you know, if you think of a horse that's trying to run on one hand we're telling the horse, you know, stop running, stop running, you're going too fast, stop doing this. And on the other hand you're also kind of whipping the horse and saying well keep running faster. That's kind of what we would do if we were giving procrit and chemo at the same time. So we don't typically do those two things together. We do give growth factors for white blood cells because at some point we want the white blood cells to come back up and not be at risk of infection. But procrit typically isn't something we use commonly because red blood cells are, you can replace them with transfusions. So we don't want to introduce another variable that stresses the bone marrow in terms of, you know, giving procrit.

 

- A lot of people ask about ivermectin also. Do you, do you have any observations on that?

 

- So I think, thank you for that question. I, you know, I think all of us are very curious about the studies with Ivermectin because I think, you know, regardless of what it is used for right now, which all we know, it's an anti-parasitic, anthelmintic drug, it's incredibly effective in doing that. And there's been a lot of sort of what we call like clinical studies, not in humans, but in cells, in animals looking to see can ivermectin actually inhibit cancer cells? And, and there are good reasons to try this, right? Because the way it kind of shuts down and gets rid of parasites, it's inhibiting certain pathways that cells could be using. The issue with ivermectin in cancer therapy is one, a parasite is a foreign body. It's not part of you, it will never be part of you. The way it uses its metabolic kind of cycle is unique to it. It is not part of your body. Cancer cells are part of your body. They use the metabolic pathways that your normal body uses, the liver cells use, the heart cells use. And so to use something that shuts down metabolic pathways in a non-human scenario with certain cells to do that in a complex being like a human being with our trillions of cells, we typically would need very high doses of ivermectin. Those kind of doses would cause our liver to fail, our kidneys to shut down because now you're targeting a very complex human being and the cells that have essentially hijacked it, right. It's our own cells that are betraying us unlike, you know, a worm that's just trying to, you know, live with us. So I think unfortunately we haven't had a lot of human studies at doses that we can tolerate that have shown promise with ivermectin. I, for one, would be very happy if we had something like ivermectin and the more therapies we have, the better. But I can't at this time say that it's shown really any promising effectiveness at the doses that we can actually take without, you know, killing one of our vital organs.

 

- Okay. Okay. How do you personally approach conversations with patients when introducing a clinical study option and where do you feel the biggest gaps still exist in terms of tools, resources, or support that could help patients better understand and feel comfortable with those discussions?

 

- That is a fantastic question. I will say it very much depends on what the person in front of me is dealing with. Do they, is their cancer diagnosis new? Have they tried standard therapies and those therapies haven't worked for them? But as I mentioned to you during my talk, I think I'm very, my approach is just to be very open and hopefully transparent about what this clinical trial can do for them, right? Because if it's a phase one trial, I want to be transparent and tell them, this drug hasn't had a lot of testing, I can't give you a lot of information if this will work for you. I can't tell you about every single side effect you may have with this drug because this is early in its testing. And that's the idea of an informed consent. You are giving the most accurate information you have, you are being ethical and what your trial that you're discussing and, and hopefully you're guiding your patient the right way and you're giving them the option to have all the information, process the information and then say yes or no based on a very personal decision. And I can tell you it is a very personal decision. I can tell the same facts and figures to one patient and they will jump at the chance to be on the trial and I can tell the same information to a second patient and they would absolutely say no because in their mind, for their life and their situation, those numbers, all of the burden it takes to be on a trial makes zero sense and they politely decline.

 

So I think, you know, being very transparent about what the trial is, the facts, the options, the treatments, they will get, honestly, the burden on people when they're on a trial because you do have to travel to a trial site, you have to do a lot more testing. But then the fantastic thing about being on a trial is it gives you an option to try something that your cancer has never seen. You have tried all these standard treatments, they haven't worked, your cancer is still outsmarting us. We need to try something different. And the trial is an opportunity to do that. Now obviously it comes with risks that we've talked about, but at least there's that option. And for me, if, you know, I always think of all my patients, it's a very personal relationship and I want them, I want the cancer to die a horrible death and I want my patients to live for as long as possible. And so to me, you know, that's sort of the conversation I have. I think the, I think we don't have enough materials, enough support, enough information, I think there's so many different things that we need to communicate what trials are to people. I think there's so much misinformation, there's so many misconceptions, but in the end it comes down to the trust between you and your care team. And if you really trust your care team and you believe that they're advocating for you and they're giving you the information you need, I hope that that is really key to presenting a trial and helping a patient understand their choices. So it's a very long-winded way of saying I think we could always use more support to help people understand trials, but it is a very individualized conversation. So I think it would be hard to create like very specific materials for every situation because it is a very personal conversation between the care team and the patient.

 

- Great, thank you. And I'm not sure if you covered this during your talk, but obviously a lot of people are interested in learning where they can find out about trials and you know, I always suggest that patients go to clinicaltrials.gov to understand more about a specific trial and they can also look up trials. At the Leukemia Research Foundation we also, on our website, do have a clinical trial matching tool that is on the website. But I wanted to address another question that came up. Are all clinical trials available at every cancer treatment center in the US or are they different at each site? And mention that that information is available where those, where each specific trial is, is available. That information is on clinicaltrials.gov. But please go ahead

 

- No, I, I agree. I think unfortunately every clinical trial is not the same at every site. Every site has its own set of clinical trials, their own portfolio for what patient population they serve so that we can help as many patients as we can of the people that we see. And so, you know what, what may be available in central Ohio at the James Cancer Hospital where I work might be different from what might be available in Florida, you know, in a smaller place where they don't see a lot of different trials and they may focus on the most common cancers they see as opposed to, you know, New York City for example. So I think it's, there's a huge difference.

 

The clinicaltrials.gov website, if you find the specific trial or trials should give you all the different places that trial is open at and it gives you contact information for whoever is leading the trial or how to get a hold of people at that place that have the trial open. It is a clunky website. Sometimes the way the trial is written, even if you go to the criteria of who can be on the trial or not, they're not always updated. So it's, I agree, it's not exactly the best way to look and find trials. I love the fact that you guys have your matching tool and a lot of, you know, foundations like the Leukemia Research Foundation and others have people that you can call and tell, you can tell them your specific situation. They're usually medical professionals, typically nurses that can then kind of say, okay, tell me more about your disease. Let me look, where are you coming from? And they can do their own kind of research and find the right trial for you. I also tell patients, don't hesitate. I get people reaching out to me all the time. They just directly email me and say, Hey, I have this, is this trial at your site appropriate? And I usually say, yea or nay and if it's not then I'm not going to waste their time making them, you know, pursue or come to a place where the trial is probably not going to, you know, help them.

 

- Right. Yeah. Okay. We have a question. Are there any clinical trials for those with no known MDS/AML mutations? Perhaps participation in an "umbrella" trial?

 

- I think if you, if you truly don't have any mutations that have ever been seen in MDS or AML, then it, I would question if you have MDS or AML because now our, we have very good technology to identify these mutations. I think if you're asking if you have a mutation that doesn't have a target, like you don't have a specific mutation that has a drug that specifically targets that mutation, you're right, an umbrella trial could have options for what we call, you know, genomically heterogeneous mutations meaning you don't have a specific target for the mutations right now, but you have other things that could work. And I think umbrella trials are great because they usually have a trial specifically for people like that.

 

- And we did in the registration, we had several people who are asking about trials specifically for their type of leukemia and in several cases a more rare form of leukemia such as CMML or you obviously you talk, you talk quite a bit about MDS because that's an area of your focus. But if you could, if you have any kind of pointers or tips about how folks with these rare forms of leukemia, what can they do? Questions they can ask, who can they turn to?

 

- Yeah, I think that's a challenge, right? Because the rarer your cancer is, there's very few centers and people that have the amount of experience and have seen enough of those cancers to actually have an idea of what treatments work. My recommendation is try to find the centers that have sort of established or published in that area because you really do want to go to a center or a person that has seen more than one of what you have. Because otherwise I would not be comfortable being treated for a really, really rare disease by somebody who doesn't have experience in that. And unfortunately that may mean it's not close to where you are. But most big places now do second opinions with telemedicine. There's all these different ways to get your case in front of people and see, hey, can you tell me, you know, what my options are? And most, most of the times people will hopefully want to be able to help.

 

One person in registration asked about GvHD clinical trials. I'm not sure if you mentioned that, but I, you know, this concept of survivorship is also really important and after the treatment sometimes, you know, these issues can persist. So any thoughts or,

 

- Yeah, GVHD clinical trials are very, I mean they're a priority for a lot of people. They're a priority for a lot of transplant programs. Not just, you know, GVHD treatment, but hopefully, you know, mitigation and maybe even prevention. So starting something right when you're about to get your transplant all the way through. I would say these are typically run by the cell therapy or the transplant teams that do the transplants. So if you have a team or a site that's doing transplants, they're the ones that usually lead these trials.

 

- Okay. And real quick, I was going to just ask this question. Are we seeing any promise in using additional meds along with standard of care treatments with TP53 mutations in AML?

 

- That's a huge unmet need right now. We have a lot of trials that are trying to do that. I think the key word is what you said, promise. I think we are, it's too early to say if they're promising. I think we all recognize that this is a very high-risk disease and that we really, really want better therapies for it. So currently there isn't some, you know, hot new thing that I can say okay, if you weren't on this trial, I would highly recommend getting on this trial. We don't have anything like that right now.

 

- Great. Okay, well we got some really fantastic questions throughout this program. I'm so happy about that. And I'm going to share my screen. Of course it's not coming up again. Sorry. Please bear with me for one moment while I bring it back up again. And I just wanted to close by saying, you know, thank you so much to everybody who participated in today's program. We apologize again for the late start, but I think we did kind of make up for lost time with some really great questions and some great answers as well. Hopefully you all agree. As I mentioned earlier, we will be sending an invitation to everyone who participated today to fill out, to complete a form that just kind of gives us some feedback on today's program.

 

I did want to highlight, if there is anybody participating today on this program, thank you so much if you have participated on a clinical trial You know, it's a very selfless act. It's so important as a part of research and we are really grateful to you all for the consideration and the effort that you go to for participation. And if anybody has any questions about clinical trials, you know, there's a lot of information on our website. I welcome you to reach out to us. I would like to thank our speaker, Dr. Borate, if you had any closing comments, I'd welcome that.

 

- Well I just wanted to thank you for this invitation and it was totally my fault that we started a few minutes late, so my apologies for that. I just think that these kind of programs are so important for us as a community to understand, you know, how to move research forward and always, always, you know, in awe and grateful for patients that give their time and literally their blood to take part in these trials. So thank you.

 

- Yeah, thank you. And finally, just one more thank you to our sponsors. We appreciate the support that we receive so that we can host programs like this. And yeah, this is just a slide that has some information for further information. I always like to share the NCCN patient guidelines link with folks. And as I mentioned, we do have quite a bit of information on our website, so please do visit the website. And thank you everyone so much for your participation. We are grateful and look forward to some great programs in the future. So have a great day. Thank you again Dr. Borate, and

 

- Thanks everyone.

 

- Hope to see you again soon. Take care.

 

- Bye.