Photo by Esther Dyson
Preparing drug for a trial
The US Food and Drug Administration (FDA) has lifted the clinical hold placed on a phase 1/2 trial of SEL24, a dual PIM/FLT3 kinase inhibitor, in patients with relapsed/refractory acute myeloid leukemia (AML).
Selvita and Menarini Group, the companies developing SEL24, agreed to continue the trial with additional provisions to its protocol.
The companies will be working with trial investigators and clinical sites to obtain institutional review board approval on the revised protocol and resume enrollment in the trial, according to Krzysztof Brzozka, PhD, chief scientific officer of Selvita.
The trial is a dose-escalation study of SEL24 in patients with relapsed and refractory AML. The study was designed to determine the maximum tolerated dose and recommended dose of SEL24.
The first patient was dosed in March 2017. The study began with a 25 mg daily dose, which was then escalated following cohort reviews.
In October, the trial was placed on full clinical hold, which meant no new patients could be enrolled on the trial, and enrolled patients could not receive SEL24 until the hold was lifted.
The hold was the result of a fatal cerebral adverse event that was considered possibly related to SEL24.
The event occurred in a patient who started treatment with a 150 mg dose of SEL24 as the third patient in this dose cohort.
The patient received 4 doses of the drug and developed a life-threatening, grade 4 venous thrombus in the brain with subsequent intracerebral hemorrhage, which required hospitalization.
The patient died in hospice 4 days later. The patient’s death was deemed possibly related to SEL24.
In response to the death, a safety report was submitted to the FDA, along with a review by the trial’s data monitoring committee.
The FDA then placed a hold on the trial and requested more safety data on patients who have received SEL24, as well as specific protocol changes and additional guidance to the study staff.
Selvita and Menarini Group complied with the FDA’s requests and agreed to revise the dose-finding scheme to a standard 3+3 design under an amended protocol.
