New clinical study for children with AML aims to kill leukemia cells and minimize cardiac damage

Imagine conquering childhood cancer, only to find out that years down the road your heart may fail. Unfortunately, many children who have battled cancer face this reality. While often lifesaving, the effects of chemotherapy treatment (drugs that kill cancer cells) can take a toll on the developing body of a child, potentially resulting in life-threatening late side effects like cardiac damage.

"You go through terrible chemotherapy, achieve remission, have a new lease on life and then your heart fails," said Dr. Todd Cooper, director of the Pediatric Leukemia/Lymphoma Program and Evans Family Endowed Chair in Pediatric Cancer at Seattle Children's. "It's not fair, and we're determined to change this reality."

Cooper is leading a new nationwide clinical trial, conducted within the Children's Oncology Group (COG), for children and adolescents with relapsed acute myelogenous leukemia (AML) to test a drug, CPX-351, which has been designed to kill leukemia cells while minimizing damage to the heart. According to Cooper, up to 30% of patients who undergo chemotherapy for AML will have late term side effects that affect the heart. For Cooper, that's 30% too many.

AML is an aggressive type of cancer that affects the bone marrow and blood. AML can be difficult to treat and requires intensive chemotherapy and often bone marrow transplantation.

Cooper says previous trials testing the effectiveness and efficacy of CPX-351 have shown tremendous promise in adults, and so he's hoping to bring that same success to pediatric patients.

Bringing hope to children with acute myelogenous leukemia
Because AML is difficult to treat, standard treatment commonly involves multiple chemotherapy medicines that are given at a higher dose in order to kill the cancer cells.

"The chemotherapy tends to be very intensive," said Cooper. "Some of the most effective medicines work really well against leukemia, but the side effects, including damage to the heart, can be severe."

CPX-351 delivers chemotherapy in a different way than standard chemotherapy. The medicines are contained in a liposomal formulation which is thought to be safer for the heart. The liposome is used as a vehicle to transport the drugs into the body and into leukemia cells in the bone marrow. We hope that by being housed inside the liposome, that less of the chemotherapy will be deposited into the heart.

In phase 3 trials for adults with high-risk, secondary AML, there was a statistically significant improvement in overall survival compared to patients who received a regimen using chemotherapy drugs delivered in the standard way. The use of CPX-351 reduced the risk of death by 31% compared to the use of the chemotherapy drugs cytarabine and daunorubicin.

"This trial not only offers hope for more children to be cured, but for more children to live longer, leading more productive lives without late term cardiac damage," said Cooper. "I am thrilled to bring this therapy to children through the trial because I want kids to have access as soon as possible to these potentially lifesaving drugs."

Although results from the trial will not be completed for a couple of years, Cooper is optimistic CPX-351 will improve outcomes for children with relapsed AML and may one day become a frontline treatment.