Published on May 4, 2020
- There are four phases to a clinical trial. Before joining one, make sure you understand what the goals, risks and benefits of that phase are.
- Whether you are newly diagnosed or have relapsed after treatment, clinical trials are relevant at all stages of therapy.
- In addition to clinical trials, myeloma experts are excited about advances in immunotherapy, CAR T-cell therapy and triplet therapy.
What are the phases of a clinical trial? When should you consider participating in one? What else do you need to know and where can you find that information? We asked these questions and more to a panel of leading multiple myeloma experts during our recent virtual town hall meeting.
Dr. Frits van Rhee and Dr. Guido Tricot, both from the University of Arkansas for Medical Sciences (UAMS) Myeloma Center, and Dr. Shebli Atrash from Levine Cancer Institute of Atrium Health, discuss clinical trials with host and patient advocate Maddie Hunter. They also share what new treatments are coming down the pipeline and which ones they're most excited about. Watch now to learn more.
This program is sponsored by Takeda, Janssen and Karyopharm. These organizations have no editorial control, and Patient Power is solely responsible for program content. It is produced by Patient Power in partnership with UAMS Myeloma Center.
Transcript | The Value and Phases of Multiple Myeloma Clinical Trials
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.
We're going to move now to a kind of treatment which is called a clinical trial. Dr. Tricot, I would like perhaps to have you at least talk a little bit about where do you think the best places are for patients to learn about clinical trials?
We basically distinguish four different types of trials. The Phase I trial is where you take all types of cancers, and you try to find the maximum tolerated dose. You don't look for efficacy, but you want to know the maximum tolerated dose. It's clear that patients who have a lot of other options still open are not candidates for this type of trials, because the probability that they will do well is extremely low, and it's very likely that they will have no response to this treatment.
That's the Phase I trial. The Phase II trial, now you go to one disease and you want to see what the efficacy is, and then you go through a phase III trial where you combine your new treatment to the best alternative treatment.
And then you have the Phase IV trial but most of the trials are Phase I, II or III and they have each their role, but people should not expect from a Phase I trial to be cured of their disease. It's extremely unlikely. It's single agent drug, which is already not good. Typically, those patients have already had multiple relapses, are fairly refractory to those drugs, and now you start with a single drug and you try to see whether they've had an impact on the disease. It typically doesn't happen in the Phase I trial.
In the Phase II trial, where you have found the dose, you can see some effects although they are usually of short duration. It's actually the Phase III trials that give us the most information, but also needs the longest to work, and the most important long-term outcomes come from those Phase III trials.
So, Dr. Tricot, that was a great explanation of the different phases in trials and how they're targeted. And, Dr. van Rhee, where in a treatment protocol do you see clinical trials, at what stage?
Dr. van Rhee:
Actually, at all stages of therapy, clinical trials are relevant. We have a trial specifically for high risk patients where we incorporate daratumumab (Darzalex) with carfilzomib (Kyprolis), up front they get daratumumab between transplant immediately after transplant and is given combination of carfilzomib, lenalidomide (Revlimid) and dexamethasone (Decadron) as a maintenance strategy. Historically with our high-risk patients, and I think this applies to all centers in this group of patients with very high-risk diseases, very difficult to tackle. And innovative approaches are needed there.
Obviously with the lower risk patients, the question is how we can safely scale back on therapy and still have excellent outcomes. And the other question there is how can we identify patients with so-called low-risk disease, who unexpectedly have an early relapse. We sometimes refer to them as the misfits, the patients who are supposed to do well and they don't. So that's an important category of patients to identify. Then there are questions about transplantation, questions about what consolidation to give what maintenance. So at every stage of therapy of up-front therapy, clinical trials are being conducted. Obviously, the relapse setting is extremely important to find efficacious drugs and drug combinations, which then later on can be incorporated in frontline approaches. So clinical trials are incredibly important at every stage of the disease.
So I urge patients to be on the lookout for an opportunity. Dr. Atrash, I'm wondering, with your patients, if they are curious about getting informed themselves and educating themselves about trials in each of these phases, where do you suggest that they look?
Oh sure. So there is the ClinicalTrials.gov is the website that has all the clinical trials all over the United States. However, it can get a little bit confusing. So if you want to make it simple, I would strongly suggest that you get a discussion with your physician. As we just discussed, each clinical trial has a different goal, so patients must understand why they are joining this trial. Some trials, as we've talked, are Phase I clinical trial. The goal is to find an effective dose so patients will not be randomized, patients will not be combined with the, we're getting drugs and multiple combinations of drugs, and if that's the goal, then that's the goal. It's completely different than a Phase II trial where you have an established dose and you're trying to either combine with something else or give it by itself.
So it's important to discuss why I'm getting into this trial? What is the downside of this if we're getting enrolled in this trial? And what's the benefits from it? To me, almost always the benefits of any clinical trials, weigh better than the losses or the downside of getting enrolled. Not only it will give us information for the future, the patients will get enrolled in the clinical trial, they will be the first to get benefits out of that drug if it is working. So if we start Phase I trial today, for example, or any monoclonal antibody today, we will not get it approved for another four or five years. But patients on clinical trials, they are already getting the benefits out of this drug. You could tell once you check with your doctor, some drugs we know they are working, we just have to prove it. We just have to make sure it's safe for the patients. So that's very important to check with your physician to see which trials are best for you and which trials are available in the center close to you.
So, that idea of having the partnership with your doctor to understand the landscape of clinical trials is really great. I know in my support group, we have members that really want to get themselves informed, they talk with their doctors, but they also look at things like SparkCures or HealthTree. These are other patient-led organizations that are looking to make it easier to try to figure out those questions that all of you have raised about, how do I know which one is right for me? Dr. Van Rhee, in terms of the clinical trials that we run, are we seeing more and more African Americans in these trials and if so, what are the success rates that you're encountering?
Dr. van Rhee:
To be frank, I think that there is still a lot of disparity in outcomes with regards to African Americans and African Americans accessing both healthcare and clinical trials. And I think that's an area where the whole myeloma community, both patient advocates, doctors and pharma really need to make an effort to make these trials more accessible to the minority populations. There are issues of health coverage, there are issues of being able to travel to a center where you can get a clinical trial, especially in a rural state like Arkansas, sometimes patients live several hours away and just getting to a center is a problem. And I think it's a very important question, and it requires a very concerted effort to improve access to clinical trials for African Americans and other minorities.
Yeah, it's ongoing problem.
Can I add something to that?
Yeah. So the studies have been done where African Americans and Caucasians got the same treatment. When they get the same treatment, they have the same outcomes. So if the outcome in African Americans is lower, it's not as good as in Caucasians, it's only due to socioeconomic issues. It has nothing to do with, "Oh, African Americans have more resistant myeloma than the non-African Americans." It has to do with socioeconomic factors, and we need to make sure that as many people as possible get optimal treatment in a situation where they can afford it and that's not always possible. It's important to know that African Americans do equally well compared to Caucasians if they get the right treatment or the same treatment.
Okay. One last question in this domain of clinical trials and things that are upcoming. What excites you about what's in the pipeline?
Dr. van Rhee:
I think the immunological therapies are very interesting. The antibodies which are currently available than the antibodies which carry a drug they're like a silver bullet. The antibody flies to the tumor and delivers a chemical there very specifically. And then there are these bi-specific antibodies, which attach to the tumor and with their other arm, grab an immune cell and activate it. And the advantage of these antibody therapies is that they're available off the shelf.
The CAR-T cells are also very exciting therapies and very innovative, but there are some logistical issues in delivering these in general for manufacturing them and undoubtedly some of these therapies are getting approved this year and will be more generally available. There have been some relapses with these CAR-T cells but also the exciting thing obviously, that we're only dealing with really the first wave of CAR-T cells and that these CAR-T cells can be made a lot better as well in future.
The results with the tandem transplants and at least two or three years of maintenance therapy with triple drugs are excellent. So you don't want to enter patients that have excellent prognosis into trials that may decrease actually their chance of doing well. When I say the results are excellent, I mean in the patients who have low-risk disease, not in high-risk disease. High risk disease patients clearly are not doing well with the present treatments. And it's absolutely justified for new patients to go on trials that address the high-risk features of the myeloma.
The prospective of the patient regarding clinical trials is completely different. So your likelihood, we were always saying start with triplet chemotherapy and avoid doublet chemotherapy. But if you have a patient with doublet, means two drugs, any two drugs you choose, if the patient achieves a complete remission with two drugs only, that's the patient.
As a physician, I can share with you that the likelihood of getting into complete remission is higher if you give three drugs, that doesn't mean two drugs cannot get you to a complete remission. I don't have a magic stick to tell whether two drugs will be good enough for you. And the same applies for achieving complete remission.
I want to reach out to the patients out there. Don't get discouraged, because yes, we know if you achieved complete remission, your likelihood of living longer is higher. But that doesn't mean every person should achieve complete remission. And I've seen cases, I'm sure all of us have seen cases where patient did not achieve complete remission, and yet they are living happily, and their disease is just stable as it is. And that's okay. And if you get a patient, even if you look at the clinical trials, they compare three drugs versus two drugs, well, if you look at the arm who got two drugs, they still don't—everybody progress immediately. Some patients can stay in remission for a very long time, but your likelihood of achieving better results is if you get complete remission. And if you do three drugs, for a patient is completely different perspective, patient is 100 percent of the data.
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