The incredible promise of Total Therapy XVII
Dr. Heym gives insight into Total Therapy XVII and why this important breakthrough in precision medicine and targeted treatment offers the promise of more cures for acute lymphoblastic leukemia and acute lymphoblastic lymphoma patients.
Meet the speaker
About Total Therapy Study XVII
Cook Children’s Hematology and Oncology Center
Cook Children’s Oncology Program
Cook Children’s Leukemia and Lymphoma
Cook Children’s Hematology and Oncology Clinical Research
Host: Hello and welcome to Cook Children’s Doc Talk. We're here today with Dr. Kenneth Heym, Medical Director of Cook Children’s Oncology Program. Dr. Heym specializes in the care of children with childhood cancers as well as being the medical director of oncology. Dr. Heym is also very actively involved in research focusing mainly on leukemia and lymphoma and has published several important works on the subject. Dr. Heym, thank you for joining us today to talk about Total Therapy Seventeen, the upcoming clinical trial for children with acute lymphoblastic leukemia or acute lymphoblastic lymphoma.
Dr. Heym: Thank you for having me here and it's my pleasure to be able to discuss this exciting work that's going to be something we can be a big part of here at Cook Children's.
Host: So can you start by giving us an overview of the Total Therapy Seventeen clinical trial.
Dr. Heym: So acute lymphoblastic leukemia is the most common disease that we treat in childhood cancer. It has gone over the years from a uniformly fatal disease to one in which the vast majority of children will not only be cured of their disease but will go on to have the rest of their life just as before. So Total Therapy Seventeen is the upcoming trial for newly diagnosed patients with acute lymphoblastic leukemia, It is through the St Jude Children's Research Hospital in Memphis Tennessee, now, we have been honored to have an ongoing relationship with St Jude for probably the past twenty years. We participated in other clinical trials with them, We were actually the only institution in the world to participate in the Total Fifteen acute lymphoblastic leukemia protocols so we were the only other hospital that participated in an up front newly diagnosed trial for children with ALL with St Jude. Total Seventeen is really going to be a summary of all that we've learned about leukemia in the last decades really trying to maximize not only the existing therapies that we have for childhood leukemia but also incorporating so much new technology and some of the really cutting edge therapies that are being used, the goal being to cure as many children as possible obviously but also to try to minimize the side effects which can occur both during therapy and long term later in life. The goal is really to try to provide individualized care to each patient.
Host: So you mentioned the long term what are the long-term risks for children?
Dr. Heym: So children who survive childhood cancer are at risk for many long term health issues. For patients with leukemia some of the more important ones are due to their exposure to steroids as children. They do have a risk for issues with bone growth and bone health they have a higher risk for something called a vascular necrosis which is kind of a type of arthritis they're also exposed to medications that can affect heart function both in the short term and long term. We know that there's a lot of data coming out that survivors of childhood ALL have an increased risk for obesity and all the health problems that are associated with that. So as more children are being cured part of the main focus of our treatment plans is to not only continue with those good survival rates but to also minimize the exposure to toxic drugs and decrease the long term late effects that patients are having. And by incorporating a lot of the newer technology and newer types of medications, which Total Seventeen will include, we’re able to remove a lot of the old type chemotherapy that really attacks the entire body and focus a lot on treatments that just will attack the leukemia.
Host: As one of the five children's hospitals participating in the trial what role does Cook Children’s play?
Dr. Heym: Well, we have had a very long established successful relationship with St. Jude participating in leukemia trials with them both for newly diagnosed patients as well as relapse patients for both acute lymphoblastic leukemia, or ALL, and acute myeloid leukemia, or AML. We are a large center here we see a large number of newly diagnosed patients with ALL and so I think we will certainly contribute a fair number of patients to the study and provide a lot of data. I also think we bring a unique aspect to the protocol in terms of the collaborating sites because we have worked closely with St. Jude before and as mentioned before we were part of the Total Fifteen protocol for acute lymphoblastic leukemia so we can serve I think as kind of an advisory role as well to some of the other collaborating sites.
Host: How is being on a Total Seventeen protocol different from being on a standard treatment regimen for leukemia?
Dr. Heym: I think participating in the Saint Jude protocol is allowing us to really provide our patients with access to all of the most cutting edge state of the art therapies for ALL, Total Seventeen will provide a patient with access to many things that may not be available otherwise. Number one is there are going to be a lot of biologic, genetic, and molecular studies being performed on the research side through Saint Jude that are going to enable us to learn much more about each individual patient's disease so that they can each be treated more appropriately and in a more personalized fashion. Being on Total Seventeen will also allow patients the potential opportunity to receive immunotherapy which allows the body's immune system to be utilized to fight the cancer itself and a lot of times will have many fewer side effects both short and long term than conventional chemotherapy. It also incorporates newer ways of using standard chemotherapy drugs that will hopefully allow them to have their maximal effect with a decrease in side effects.
Host: So, how do genetics affect the way children and young adults tolerate and respond to the treatment of childhood ALL and LLy?
Dr. Heym: So genetics are really playing such an important role. We've known for years that the genetics of a patient's leukemia give us insight into how aggressive the leukemia is going to be and how it needs to be treated. We actually will put patients into different risk categories based on the genetic aspects of their leukemia. We're also learning though is that the different genetic make up that all of us have affects our ability to tolerate chemotherapy drugs, how we break those drugs down, and we also know that there are certain genetic changes seen in people that will make them more prone to having side effects from specific chemotherapy drugs. So as part of Total Seventeen in addition to the therapy aspect there's also going to be testing looking for some of these genetic changes that might identify children that are going to be at higher risk for having potentially life altering side effects so that their doses can be adjusted appropriately and they can still get the anti leukemic effect that's desired but that they'll be at much less risk for developing some of the debilitating side effects that can occur later on.
Host: So can you talk a little bit about how precision medicine can, one, further reduce the risk of recurrence and, two, reduce the short and long term side effects of treatment?
Dr. Heym: So individualized therapy or precision medicine really is nowhere better utilized than in acute lymphoblastic leukemia. There are certain clinical and genetic factors that for decades we've been using to really put patients in a specific risk category so they can get what we thought of back then as individualized therapy. As we're learning much more about the specific genetic make up of not only leukemia but of each individual patient and how they're gonna react to specific medications and their risk for side effects we are really able at this point now better than ever before and I think with the resources and the research going on at St Jude here at Cook we will be able to as part of Total Seventeen provide precision and personalized medicine for ALL patients in a way that more standard therapies cannot. And so we will be doing a lot of testing that will not only identify how aggressive the leukemia is going to be and how we will need to be treated but also which drugs and in which doses are going to be the most important and the most appropriate for individual patients. The ultimate goal of this obviously is to cure as many patients as possible but we also, and I think just as importantly, we don't want to just care patients if they're going to be so debilitated from their therapy we want their life to be as full and normal as it can be and so I think with this precision approach the goal is simply to give each patient as much therapy as they need but no more.
Host: Are there any initial case studies or patient family testimonials at this point?
Dr. Heym: Well, Total Seventeen has been open at St Jude now for quite some time and so far it has been as successful as all the preceding Saint Jude studies. We have had many patients here at Cook Children’s that have participated in St Jude trials as part of our collaborations that have had you know incredible success in response and as mentioned we were the only other institution to participate in the Total Fifteen protocol. And, we have many patients here who we are following now many years off therapy who are disease free who clearly benefited from the questions that were being asked for that treatment. And so we're very excited to be able to continue our collaboration with St Jude because it is really allowing us to provide our patients with the most cutting edge therapies. We know that how we're going to be treating here Cook Children’s is second to none.
Host: When does this trial open and who is eligible for the trial?
Dr. Heym: We are in the process of kind of negotiating all of the final aspects of getting the protocol approved at Cook Children’s. There was already an amendment at Saint Jude so they are already working to try to improve the protocol even though it has been open very long they're very attuned to making changes in real time. We are hoping that the protocol will open and will be able to start enrolling patients potentially as early as September or October of this year. And this will be a trial … one of the reasons it's called Total Therapy is because other organizations will break up protocols for patients with acute lymphoblastic leukemia into high risk protocol, low risk protocol, and T-cell ALL protocol, the St Jude protocol is all encompassing and so, all newly diagnosed patients older than one year of age at diagnosis with acute lymphoblastic leukemia, all types will be eligible for the protocol. And so we think we'll be able to have many patients participate that will enable us to learn even more about this disease and how we can treat these patients better.
Host: So what do you expect or hope for in terms of the outcomes from this trial?
Dr. Heym: I think if you were gonna simply ask what the ultimate outcome would be it would be obviously that we are going to cure more patients with childhood acute lymphoblastic leukemia than ever before. The cure rates for ALL continue to increase. The St. Jude Total Fifteen protocol that we participated in at the time it was published produced the highest cure rates for a child today with ALL. So I think the simple goal is to cure as many kids as possible, but I think, as mentioned before, just as important we want to try to minimize the side effects that these patients experience because sometimes you will cure a patient's leukemia but they will have devastating debilitating issues that they're gonna have to deal with the rest of their life. So I think by utilizing the newer types of treatment, namely immunotherapy, cellular therapy, and also trying to individualize how we dose chemotherapy and assign chemotherapy based on genetic factors I'm hoping that not only will the majority of children continue to survive but that they will be leading as active and fulfilling and really have their lives be minimally if at all limited by what they went through as a child.
Host: So I have one last question before we close which is why should I, or anyone really, care about this trial?
Dr. Heym: I think this is a trial that everyone should care about because the hope is, and if we continue to follow suit with our relationship with St Jude, that again the vast majority of children with acute lymphoblastic leukemia will continue to be cured I think that we should also care locally because here at Cook Children’s we are going to be able to continue to provide our ALL patients which is the majority of our oncology patients with therapy that is unparalleled anywhere else. This is going to be a treatment that will allow our patients access to the most state-of-the-art, up-to-date modern therapies. And so we don't have to feel that any of our patients are gonna need to go to another institution to get something they need. We are really going to be able to provide the patients in our local region and also our referral base with therapy for ALL that is really second to none.
Host: Dr. Heym, we really appreciate you taking the time to talk to us today about this very important advancement in caring for children with acute lymphoblastic leukemia and lymphoma and thank you for all you do here at Cook Children’s and for kids everywhere.
Dr. Heym: Well, thank you for having me. It's a pleasure and we're very excited about what we're able to do here and only know that things are going to improve in the future.
Host: We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children’s dot org.