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Massey researcher awarded nearly $1 million to develop a clinical trial to test a new AML therapy

Steven-Grant

VCU Massey Cancer Center researcher Steven Grant, M.D., was awarded nearly $1 million in grant funding from the National Center for Advancing Translational Sciences (NCATS) to support the development of a clinical trial that will test a novel, experimental therapy for acute myeloid leukemia (AML, an aggressive blood cancer) that he co-discovered.

The therapy combines the investigational drugs AZD1775 and belinostat and is based on research conducted in Grant’s laboratory and spearheaded by Yun Dai, M.D., Ph.D.  Their pre-clinical research found that AZD1775, a Wee1 inhibitor, interacts reciprocally and synergistically with pan-HDAC inhibitors (e.g., belinostat) to kill human leukemia cells. Wee1 inhibitors are designed to disrupt the function of the Wee1 protein kinase (which helps to regulate the cell cycle) and to cause tumor cells to divide without undergoing the normal DNA repair process, ultimately leading to tumor cell death. HDAC inhibitors represent a class of compounds that interfere with the function of histone deacetylases, enzymes which regulate chromatin structure and gene expression in tumor cells. Significantly, Wee1-HDAC inhibitor interactions spared normal hematopoietic progenitor cells (blood cells that give rise to other normal blood cells), and improved survival in mouse AML models.

“I am grateful to receive this generous support from the NCATS,” said Grant, who is the Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, co-leader and member of the Developmental Therapeutics program and member of the Cancer Cell Signaling program at VCU Massey Cancer Center and professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine. “This funding will directly support the translation of our research discovery into a clinical trial that will begin to examine the therapy’s potential for treating an aggressive blood cancer.”

Massey is developing a phase 1 clinical trial to test this combination therapy. The trial will be led at Massey by medical oncologist and researcher Danielle Shafer, D.O., a member of Massey’s Developmental Therapeutics research program and assistant professor in the VCU Division of Hematology, Oncology and Palliative Care. In this trial, Massey will collaborate with other cancer centers, including the Moffitt Cancer Center in Tampa, FL, Vanderbilt-Ingram Cancer Center in Nashville, TN, and Rutgers Cancer Institute of New Jersey in New Brunswick, NJ.  The goals of the trial are to identify the maximum tolerated dose for this drug regimen in patients with refractory/relapsed AML, chronic myeloid leukemia in blast crisis (CML-BC), intermediate-2 or high-risk myelodysplastic syndrome (MDS) and selected previously untreated poor-prognosis patients with AML.

Funding for the trial is supported by a UH2/UH3 grant from the NCATS,  one of 27 institutes and centers at the National Institute of Health (NIH), through its Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) program.  Grant’s team was one of four academic research groups awarded this funding aimed at testing a selection of partially developed investigational drugs (also known as pharmaceutical industry assets) for new therapeutic uses. The other awarded projects are aimed at finding therapies for glioblastoma (one of the most aggressive brain tumors in adults), Type 2 diabetes and Chagas disease (a neglected tropical disease that causes heart, digestive and neurological problems).

For every drug that is approved by the U.S. Food and Drug Administration (FDA), many others are not approved due to lack of effectiveness in treating the disease they were designed to target. NCATS leads initiatives to repurpose some of these assets to treat new disease indications and deliver more treatments to greater numbers of patients more quickly.

Each award recipient will test a selected asset for its effectiveness against a previously unexplored disease or condition. The industry partner for the trial at Massey is AstraZeneca.

“The New Therapeutic Uses program helps re-engineer the research pipeline by crowdsourcing pharmaceutical company assets that already have cleared several key steps in the development process, including initial safety testing in humans,” said Christine M. Colvis, Ph.D., NCATS director of drug development partnership programs. “This approach enables scientists nationwide to contribute their expertise to accelerate the pace at which discoveries are turned into treatments and cures for patients.”

The pilot phase of the New Therapeutic Uses program tested the utility of template agreements established with each industry partner that proved successful in facilitating negotiations. The agreements reduced the time required to establish collaborations between industry and academia to about three months from the more typical nine months to one year.

NCATS leads the New Therapeutic Uses program with additional scientific expertise provided by the National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Aging; National Institute on Alcohol Abuse and Alcoholism; and National Institute on Drug Abuse. For more information about the NCATS program, visit the New Therapeutic Uses webpage.

The trial is expected to open at Massey soon. Those interested in enrolling or learning more about this clinical trial should contact Massey’s Clinical Trials Office at (804) 628-2364 and reference the AZD1775+belinostat trial.

Massey is currently conducting more than 100 total trials on a variety of cancers. View a complete list of all active clinical trials available at Massey.

Written by: Jenny Owen

Posted on: September 2, 2015