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Researchers hope trial of CPX-351 produces ‘huge win’ for children with AML
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A clinical trial is underway within the Children’s Oncology Group to assess the efficacy of CPX-351 in children and adolescents with relapsed acute myeloid leukemia.
Previous research demonstrated the safety and efficacy of CPX-351 (Vyxeos, Celator) — a nanoscale co-formulation of cytarabine and daunorubicin — in adults with AML. Researchers now hope to achieve the same results in the pediatric population.
“Chemotherapy for relapsed AML is very intensive. Some of the most effective medicines that work really well against leukemia also have significant side effects, including damage to the heart, which can be severe,” Todd M. Cooper, DO, director of the pediatric leukemia/lymphoma program and Evans family endowed chair in pediatric cancer at Seattle Children’s Hospital, said in a press release. “This trial not only offers hope for more children to be cured, but for more children to live longer, leading more productive lives without long-term cardiac damage. I am thrilled to bring this therapy to children through the trial because I want children to have access to potentially lifesaving drugs that may decrease damage to their heart.”
HemOnc Today spoke with Cooper about the study and why he thinks the findings in adults will translate to pediatric patients.
Question: Why did you choose to assess CPX-351 in pediatric patients?
Answer: I have been involved with the Children’s Oncology Group (COG) for some time now, and I am the chair of the new agents committee of the COG AML group. We are always looking for the most promising new agents — not only the most effective agents, but those that are well tolerated and can address other important issues experienced by children with AML. One of the most important issues is the fact that children who are treated for or cured of AML have a great deal of cardiac toxicities from anthracycline. CPX-351 contains the most commonly used drugs, cytarabine and daunorubicin, which are contained within a liposome. This is thought to be cardioprotective and have properties that allow these agents to be more effective due to increased exposure of the leukemia cells to the agent.
Q: What type of efficacy and safety has t his agent demonstrated in adults?
A: CPX-351 has been in development for some time now in adults, and there is a determined maximum tolerated dose. There has also been more than one phase 2 study looking at the efficacy in both relapsed patients and in adults with newly diagnosed AML, and the agent demonstrated efficacy in both populations. A phase 3 study compared non-liposomal encapsulated cytarabine and daunorubicin vs. CPX-351 in patients with high-risk AML and myelodysplastic syndrome. Results, presented at last year’s ASCO Annual Meeting, showed CPX-351 demonstrated superior OS, a comparable safety profile, and improved 30-day and 60-day mortality rates compared with non-liposomal–encapsulated cytarabine and daunorubicin. This has helped us to move this forward in children.
Q: Why do you and your colleagues think these findings will translate to pediatric patients?
A: We often look at the adult experience and try to become involved in new agents that are safe and effective in hopes that they will have the same results in children. We also hope that the agent has a cardioprotective effect in children. Although pediatric and adult AML are biologically different, this agent does use cytotoxic chemotherapy that is effective no matter the biological profile. It is very translatable to children. We are looking for an agent that has efficacy that is comparable or superior to that of current treatments, while still offering hope for decreased cardiotoxicity. From an efficacy standpoint, I think it will translate to children because we know these agents work. An initial, single-institution phase 1 clinical trial conducted at Cincinnati Children’s Hospital demonstrated that the adult maximum-tolerated dose is also tolerable in children.
Q: How many children will be enrolled , and what is the study timeline?
A: This study is being conducted within the COG, and there are two parts to the study. One part is the small safety lead-in to ensure that the particular dose we will use in children is safe. The dose used in this COG study is one level higher than used in the single-institution study at Cincinnati. We wanted to use an anthracycline dose comparable to those used in other pediatric studies. We now move on to the efficacy portion, which will enroll about 40 children. We expect to take about a year or less to enroll all 40 patients.
Q: Can you describe the potential impact of this study?
A: This study could potentially change our standard of therapy and improve late cardiac outcomes for children with AML.
Q: Once this trial is complete, is there a plan for additional research?
A: If the agent is found to be safe and efficacious, we plan to move this into our upfront phase 3 randomized study within the COG that enrolls about 1,300 children. We will test CPX-351 in the first two courses of therapy, compare it with our current standard of therapy, and determine whether it is at least efficacious or better. This also will allow us to do very intensive cardiac monitoring of a large number of children in order to compare CPX-351 with non-liposomal standard therapies we are using.
Q: Is there anything else that you would like to mention?
A : This study is providing a unique opportunity — to be able to prospectively test an agent that we already know works in adults and to be able to mitigate some of the side effects that are so severe in children, most notably the cardiac side effects. In the past, AML in children and adults has been very difficult to cure. Although we have improved cure rates and OS is now more than 65%, this comes at a heavy price in terms of late side effects. If we can continue to improve upon these survival rates while also mitigating the awful late side effects, this would be a huge win for children who have to deal with this, as well as their families. – by Jennifer Southall
References:
Absalon M, et al. Abstract 10541. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Lancet JE, et al. Abstract 7000. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
For more information:
Todd M. Cooper, DO, can be reached at Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105;email: todd.cooper@choa.org.
Disclosure: Cooper reports no relevant financial disclosures.