Fighting a formidable leukemia with an expansive clinical trial

The best available treatment for acute myeloid leukemia is a drug combination established more than 30 years ago. And today less than a third of newly diagnosed AML patients survive beyond five years. An ambitious clinical trial announced this week aims to speed up the search for new treatments by matching patients with one of several different drugs selected to block a specific tumor mutation or signaling pathway.

“What we’re trying to do with the master trial is to take the knowledge of individuals’ leukemias and match them to current therapies,” said Brian Druker, M.D., director of the OHSU Knight Cancer Institute and a leader of the AML trial.

“Right now it’s a one size fits all. If you are diagnosed with AML, you get standard chemotherapy,” he said. “We are now learning there are 20, maybe 30 types of AML. We shouldn’t be treating them all the same.”

The study emerged from Beat AML, a collaboration started in 2013 by The Leukemia & Lymphoma Society and the OHSU Knight Cancer Institute. Similarly designed umbrella trials are underway in lung cancer (Lung-MAP), colorectal cancer (FOCUS 4), and melanoma (SU2C-Melanoma Research Alliance), to name a few.

VIDEO: Brian Druker, M.D., talks about his hopes for the Beat AML Master Trial.

The Beat AML Master Trial will be open to people age 60 and older who have been newly diagnosed. Researchers will take a bone marrow sample and complete a gene sequencing analysis within seven days. Patients whose cancers have genetic markers that can be targeted will be assigned to receive personalized therapy. If no such “actionable” genetic findings are found, the study will offer therapy with an investigational drug with broad activity against AML.

As it stands, the study has four targeted-therapy arms testing the following investigational drugs: samalizumab (Alexion), BI 836858 (Boehringer Ingelheim), enasidenib (Celgene), and entospletinib (Gilead Sciences). The Leukemia & Lymphoma Society said it expects the study to expand to as many as 10 different treatments.

The nonprofit’s leadership has helped bring competing pharmaceutical companies into the collaboration. “They aren’t a drug company who’s pushing a specific drug,” Druker said. “They’re trying to improve the outcome for all patients with this leukemia regardless of where the drugs come from. So they are a perfect neutral broker.”

Enrollment of subjects is taking place at the OHSU Knight Cancer Institute and four other centers: The Ohio State University Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center. The Leukemia & Lymphoma Society said six more cancer centers are prepared to begin enrolling patients in April, and the trial will eventually expand to between 15 to 20 sites.