AT ASH 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – A multi-arm clinical trial aims to transform the treatment of acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially unchanged for 4 decades.

Launched in October 2016, the multicenter BEAT AML Master Trial is based on a simple but radical goal – turn around genomic tests of bone marrow biopsies within 7 days to allow targeted therapy, said lead investigator Brian Druker, MD , of Oregon Health and Science University Knight Cancer Institute in Portland.

This strategy reflects the central challenge of acute myeloid leukemia (AML), which is not a single disease, but a group of at least 10 cancers driven by distinct, targetable mutations, said Dr. Druker, whose work on imatinib helped to pioneer precision medicine in cancer.

Speaking at a press conference at the annual meeting of the American Society of Hematology, he emphasized that rapid, accurate genomic testing is the only way to prescribe targeted agents for AML in time for them to help patients. “It really is about matching the right patient with the right drug,” he said. He also spoke about AML in a video interview at the conference.

That is a major departure from the current approach to treating AML, in which patients receive standard chemotherapy regimens that are toxic and largely ineffective. “Patients themselves call this barbaric therapy,” said John Byrd, MD , who is co-leading the trial on behalf of the Ohio State University Wexner Medical Center in Columbus. “In this trial, we’re going to move away from toxic therapy that is not potentially curative to give more targeted medicine instead.”

In addition to Dr. Druker’s and Dr. Byrd’s centers, Memorial Sloan Kettering Cancer Center, New York, and Dana-Farber Cancer Institute and Massachusetts General Hospital, both in Boston, are onboard for the study. The lead investigators hope to add another six centers to the study group and to have 10 arms of the study underway by mid-2017.

Older patients with AML find chemotherapy especially hard to tolerate and typically respond poorly. Accordingly, the trial will enroll those aged 60 years and up regardless of their genomic profile, the researchers said. Patients lacking targetable markers will be offered investigational therapies showing broad activity in AML.

Another complexity of AML is that any patient can have a variety of mutations, including some affecting only a small subset of leukemia cells, Dr. Byrd noted. Targeting those mutations cannot eradicate disease, but past trials did not rank or choose therapies based on mutation prevalence. Thus, this trial is the first to ask “which mutation is in all of the cells, which gives you the opportunity to get rid of all the disease,” he emphasized. Again, patients – not individual markers or agents – are the priority.

The study also is meant to be nimble – arms can be quickly opened or closed if bench or clinical data are promising or lackluster. This design does not preclude FDA approvals, said Louis J. DeGennaro, PhD , of the Leukemia and Lymphoma Society, which is sponsoring the trial. “We have worked closely with FDA to design a unique protocol that we believe will change the paradigm of AML treatment and future clinical trials,” he added. “This is an unprecedented collaboration.”

Dr. Druker agreed. “If we do this correctly, we can potentially see large effects, and that can become the impetus for rapid FDA approval of these drugs for the right patients,” he said. “That one of the things this trial is designed to do.”

Dr. DeGennaro is president and chief executive officer of the Leukemia and Lymphoma Society, which is sponsoring the BEAT AML Master trial. Dr. Druker disclosed ties to a number of pharmaceutical companies. Dr. Byrd had no relevant disclosures.