VCU's Massey Cancer Center Leads Study of Promising New Compound
Bryostatin 1 to Be Used in Combination with Chemotherapy Against Relapsed Leukemia

Richmond, VA. A new Phase II study will evaluate a promising new compound that will be used in combination with conventional chemotherapy to fight relapsed acute myelogenous leukemia, a life-threatening disease. Steven Grant, M.D., with Virginia Commonwealth University’s Massey Cancer Center, is leading the multi-center trial that includes six sites.

In one of the first large-scale trials of its kind, an experimental compound known as bryostatin 1 will be combined with high-dose chemotherapy to attack the signaling pathways that protect leukemia cells. Grant’s research with bryostatin 1 began nearly 10 years ago, when it first showed promise in the National Cancer Institute’s marine product discovery program. Since that time he has brought bryostatin 1 through laboratory studies and into clinical trials.

The white blood cells of patients with acute leukemia grow rapidly but do not mature properly. With about 11,500 new cases diagnosed yearly, about 65-70 percent of patients with acute leukemia respond to initial therapy and enter remission. However, the majority of these patients relapse and will ultimately die of their disease.

"Relapsed acute leukemia is very difficult to treat," said the Massey Cancer Center’s Grant, professor of oncology in VCU’s School of Medicine and lead researcher of the multi-center study. "The majority of these patients have a very limited survival they will not respond to today’s standard treatments and will die of their disease. While there are numerous experimental approaches being evaluated, there is no universally accepted treatment approach."

Derived from the sea creature bugula neritina, which grows in stringy brown colonies that resemble algae, bryostatin 1 is a prototype of a new group of anti-cancer agents known as signal transduction modulators. Grant’s previous research has shown that bryostatin 1 activates an enzyme in human cells that plays a key role in triggering a number of functions including cell division and maturation.

"Healthy cells are programmed to stop multiplying and to die at a certain point, through a built-in 'suicide' program," said Grant. "However, cancer cells continue to live and multiply far beyond the normal life-span. Bryostatin 1 appears to lower the threshold for cancer cell suicide and at the same time stimulates the growth of normal bone marrow cells potentially a considerable benefit in the treatment of leukemia."

Of the 30 patients who enrolled in Grant’s Phase I AML study, five experienced complete remissions. This is an unexpectedly positive result for a Phase I study, which is only the first step in the lengthy drug approval process and is designed to determine safe dosage levels rather than measure effectiveness.

Grant’s current AML study was funded recently by the NCI with a $706,000 award. He hopes to enroll a total of 50 adult patients through the study’s six participating sites. In addition to the Massey Cancer Center, sites include: the M. D. Anderson Cancer Center in Houston; New York City’s Columbia-Presbyterian and New York Hospital-Cornell medical centers; the University of Pittsburgh; and Wake Forest University in Winston-Salem, N.C. With enrollment expected to begin in the next two months, Grant already has received inquiries from patients and physicians in Wisconsin, Maryland and Canada.

Bryostatin 1 has shown promise in the laboratory against other types of leukemia as well as solid tumor cancer cells. Grant also is leading a Phase I, three-center study to evaluate the use of bryostatin 1 in combination with chemotherapy to treat patients with progressive chronic lymphocytic leukemia and relapsed non-Hodgkin's lymphoma. More than 40 patients have been enrolled through the trial’s three centers, which include, in addition to VCU’s Massey Cancer Center, Fox Chase Cancer Center in Philadelphia and New York Hospital-Cornell Medical Center.

VCU’s Massey Cancer Center has received continuous funding from the National Cancer Institute since 1975, when it became the first center in Virginia to be recognized as an NCI-designated clinical cancer center. The only center in the Richmond area to have received this designation, the Massey Cancer Center has attracted more than $28 million in grant funding this year, including more than $24 million in peer-reviewed funding from sources such as the NCI, the American Cancer Society and the National Science Foundation.