LLS launches collaborative clinical trial for acute myeloid leukemia

Beat AML was announced yesterday by Vice President Biden, along with many new, Moonshot inspired initiatives across industry, non-profit and government.

AML is the most lethal of the blood cancers, which together are the third leading cause of cancer deaths in the U.S.; AML is responsible for more than 10,000 deaths each year. Despite advances in treating other blood cancers, the standard of treatment for AML – a combination of toxic chemotherapies – has remained the same for more than 40 years.

Overall prognosis remains poor, with a five-year survival rate below 20 percent for patients over age 60.

With support and guidance from the U.S. Food and Drug Administration (FDA), and LLS as the sponsor, the ambitious Beat AML Master Trial seeks to change the paradigm for how this deadly cancer is treated, using an innovative precision medicine protocol.

This approach will employ comprehensive genomic profiling (CGP) to find and match specific AML genetic mutations in newly diagnosed patients over age 60, with an investigational drug or drug combination potentially best suited to attack the specific molecular mutations causing the cancer.

According to Louis J. DeGennaro, Ph.D., LLS President and CEO, “The Leukemia & Lymphoma Society is uniquely qualified to lead this unprecedented clinical trial collaboration, rare for a non-profit and a first for LLS. Beat AML, as we have named this Master Trial, showcases LLS’s stature in the cancer ecosystem,” he explained.

“It demonstrates our ability to convene the medical and research communities to think and act boldly in the quest for new and better treatments for blood cancer patients, and our aim to accelerate the rate at which precisely targeted breakthrough therapies reach the patients who urgently need them.”

Beat AML is a Unique Approach
The protocol for the Master Trial is unique in these key ways:

• The Beat AML Master Trial is among the first cancer clinical trials to be led by a nonprofit health organization. As a neutral party, LLS eases the way for multiple pharmaceutical companies to bring their drugs into the collaboration, allowing for different subtypes of AML to be treated simultaneously. Having a single master protocol will allow for a more efficient, nimble process and allows the protocol to adapt rapidly as new drugs enter and others leave the trial.
   
• Patients will be newly diagnosed, in contrast to most AML trials designed for relapsed/refractory patients. AML patients who relapse from their treatment tend to have far more genetic mutations, so identifying the genetic mutations early may offer a better chance for successful treatment.
   
• Trial design ensures both speed and sophistication between diagnosis and treatment. Typically, most AML patients are rushed into standard treatment immediately upon diagnosis. In the Beat AML Master Trial, newly diagnosed patients will have their genomic data analyzed within seven days so they can be entered into the appropriate study arm. LLS and the American Society of Hematology are working closely to educate physicians about the safety and importance of this innovative Master Trial.
   
• To ensure the patient's voice is heard, the trial protocol also will include patient-reported outcomes as a measure of success, which is a recommendation of the White House Cancer Moonshot Blue Ribbon Panel Report.

A Collaborative Approach to Precision Medicine

In conjunction with the LLS research team led by Amy Burd, Ph.D., Beat AML showcases the strong commitment to collaboration of leading AML experts, eager to put patients first. Lead investigators include John Byrd, M.D., The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Brian Druker, M.D., OHSU Knight Cancer Institute, and Ross Levine, M.D., Memorial Sloan Kettering Cancer Center, all of whom have worked closely with LLS to plan and design the master protocol for the trial.

The trial will launch initially at five leading cancer centers – The Ohio State University Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, OHSU Knight Cancer Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center and start with four treatment "arms."

The first patients are expected to be enrolled by December 2016. Six additional clinical sites are prepared to begin enrolling patients in April, and the trial will eventually expand to between 15 to 20 sites, and up to 10 different treatment arms.

LLS anticipates that 500 patients will be treated in the Master Trial. Once enrolled, trial duration for patients will range from one to three years.

Four biopharmaceutical companies – Alexion, Boehringer Ingelheim, Celgene, and Gilead Sciences – are participating in the Beat AML Master Trial, offering the following investigational drugs, respectively: samalizumab (ALXN6000), BI 836858, enasidenib (AG-221/CC-90007), entospletinib, none of which are yet approved.

Many other pharmaceutical companies have expressed interest in joining the study, and additional treatment arms may be added over time.

Other Beat AML Master Trial collaborators include: Foundation Medicine, a leading molecular information company, which will utilize its proprietary comprehensive genomic profiling assay for hematologic malignancies, for all of the patients; INC Research, a clinical research organization, which is helping LLS manage the logistics of the trial; Protocol First, providing a novel web-based digital application to help guide the clinicians; and myClin, providing a clinical trial knowledge platform to streamline communications between the clinical trial sites and maintain a high level of engagement and regulatory compliance.

LLS: A History of Leading the Fight Against AML

As the world's largest voluntary health agency dedicated to fighting blood cancer, LLS has been funding AML research since our inception in 1949.

Approximately 26 percent of LLS's current research budget is invested in AML research. Beyond the Beat AML Master Trial, LLS has invested nearly $100 million over the past five years alone to better understand and treat this disease.

For example, LLS had the vision to make a "down payment" for patients with AML in 2009 by partnering with Celator Pharmaceuticals (acquired by Jazz Pharmaceuticals in 2016) to advance its investigational drug CPX-351, an innovative formulation of two existing therapies, which recently outperformed standard therapy in a Phase 3 trial of patients with secondary AML, a high-risk subset of the disease. This investment has the potential to become the first new treatment approved in the US for AML patients in 40 years.

"Throughout our 67-year history, LLS has time and again taken a leadership role when it has recognized a challenge for patients. We're doing it again with the Beat AML initiative, working together to advance new therapies and improve outcomes for these patients who desperately need new and better options," said DeGennaro.