A specific type of drug-resistant, relapsed pediatric cancer is the focus of a new clinical trial at St. Jude Children's Research Hospital.
The phase I/II clinical trial called RAVEN aims to research a new treatment option for children with relapsed acute lymphoblastic leukemia (ALL) — a severe cancer of blood and bone marrow that attacks white blood cells.
According to Dr. Seth Karol, the trial's principal investigator and St. Jude associate faculty member, RAVEN uses a combination of traditional medicine and two newer chemotherapy medicines, venetoclax and navitoclax. Through the trial, he said they hope to better understand the impact of this combination treatment for relapsed ALL and potentially come up with a new treatment option.
"What this trial does is it uses a combination of chemotherapy medicines, that we've used for many years, with two newer chemotherapy medicines," he said, "and we hope that the addition of these new medicines will enable us to successfully treat more children whose leukemia has come back or relapsed."
Karol explained that treatment options for most children with relapsed ALL, including chemotherapy and CAR T-cell Therapy, work on the cells' surface, targeting specific proteins. However, the leukemia cells sometimes get rid of that protein and start to resist treatment. The combination of medicines used in this trial could work on these cells to reverse the drug resistance and help the cells respond to the chemotherapy drug.
"One of the things that we're very excited about this trial is that it effectively offers therapy for children who, because of the way their leukemia has evolved in response to treatments, may have lost other treatment options," Karol said.
The trial presents a "unique opportunity," he said, where researchers can gain clinal insight into how the medicines work, in terms of how successful they are and what their side effects may be, and also understand "on a more biological level" which patients respond to it.
"That will open the door to future studies that can [effectively] target patients with medicines that will work well for them as well as help [researchers] to understand how to create new combinations of treatments or even new medications completely to better treat children with relapsed leukemias," Karol said.
The trial will begin at St. Jude, and researchers there will soon collaborate with hospitals across the country and eventually even overseas with hospitals in Australia and New Zealand.
The trial has received some funding from the Hyundai Hope on Wheels Foundation for biology studies and lab work to understand leukemia cells and patient response. However, most of the funding still comes from ALSAC, the fundraising and awareness organization for St. Jude.
A similar trial was conducted internationally recently, Karol said, and St. Jude was a part of it, where 47 individuals, including 12 children, were given this medicine combination and they showed positive results.
"We were really happy with how those children responded as a whole," he said. "We were happy enough that we thought that this drug combination looked very interesting, and we thought it was important to study it further."
Karol said that RAVEN would be the first trial of its kind exclusively for children.
To be eligible for the trial, a potential candidate should be between four and 22 years old, diagnosed with relapsed or refractory ALL, and not have any prior exposure to navitoclax. A complete list of eligibility criteria can be found here.
