NEW YORK (Dec. 8, 2008) -- Preliminary results of a pivotal Phase 2 clinical trial of pralatrexate (PDX), a drug that partially works by mimicking folic acid, showed a complete or partial response in 27 percent of patients with recurrent or resistant peripheral T-cell lymphoma (PTCL). PROPEL (Pralatrexate in patients with Relapsed Or refractory PEripheral T-cell Lymphoma) findings were presented by the study's principal investigator, Dr. Owen A. O'Connor of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital, at the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco.
The international, multicenter PROPEL trial is the largest ever conducted in patients with peripheral T-cell lymphoma -- a biologically diverse group of blood cancers that account for as many as 15 percent of non-Hodgkin's lymphoma (NHL) cases in the United States. There are currently no pharmaceutical agents approved for use in the treatment of either first-line or relapsed or refractory PTCL, and average five-year survival is approximately 25 percent.
"These results indicate that pralatrexate produces a major durable response in patients for whom numerous prior treatments have been unsuccessful," says Dr. Owen A. O'Connor, director of the Lymphoid Development and Malignancy Program and chief of the Lymphoma Service at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital and Columbia University Medical Center, and associate professor of medicine at Columbia University College of Physicians and Surgeons.
Prior to enrolling in the trial, eligible patients had received a median of three (range of 1 to 12) prior systemic treatment regimens, including 16 percent of patients who had previously undergone an autologous stem cell transplant.
"Presently, there are no FDA-approved drugs for patients with PTCL, whether it is in the front-line or for patients with relapsed or refractory disease. This underscores the need for new therapies to treat this challenging disease. Pralatrexate has the potential to play a clinically meaningful role in the treatment of these patients," adds Dr. O'Connor. Pralatrexate, designed to look like the natural vitamin folic acid, disrupts DNA synthesis in tumor cells. The drug is designed to selectively accumulate in tumor cells, after which it then induces programmed cell death, or apoptosis, in the cancer cell.
A total of 109 evaluable patients received 30 mg/m2 of pralatrexate intravenously once every week for six weeks followed by one week of rest per cycle of treatment. Patients also received vitamin B12 and folic acid supplementation. Response was assessed using standard International Workshop Criteria (IWC).
In the trial, 69 percent of patients who responded did so after cycle one of therapy. The median duration of treatment in responding patients was 179 days at the time of this analysis. The duration of response exceeded three months in 17 of 29 responders (59 percent), including 6 of the 17 patients who continued on treatment. An accurate estimate of the median duration of response cannot be reported at this time due to the current length of follow up. Patients will continue to be followed until the median duration of response can be accurately estimated.
The PROPEL trial is organized by Allos Therapeutics Inc., the maker of the drug. Since PROPEL has been given fast-track status, the company will submit pralatrexate for FDA approval once the Phase 2 data has been finalized -- sometime in the first half of 2009.
Pralatrexate was developed by a team of researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) and the Southern Research Institute, including Dr. O'Connor, while at MSKCC. Dr. O'Connor and his colleagues identified the unique activity of pralatrexate in patients with lymphoma. Dr. O'Connor has continued to study pralatrexate at NewYork-Presbyterian/Columbia, now focusing on determining how the drug works in T-cell lymphoma, and on how best to combine it with other drugs to improve the treatment of patient with hematologic cancers.
Peripheral T-Cell Lymphoma
According to the American Cancer Society, approximately 66,000 patients are expected to be diagnosed with non-Hodgkin's lymphoma in the United States in 2008. Annual prevalence is estimated to be approximately 9,500 patients. In addition to the 30 to 50 percent of PTCL patients that do not respond to first-line treatment, a significant number of first-line multi-agent chemotherapy responders relapse or become refractory after treatment.
Allos Therapeutics Inc.
Allos Therapeutics is a biopharmaceutical company focused on developing and commercializing innovative, small-molecule drugs for the treatment of cancer. The Company's lead product candidate, pralatrexate (PDX), is a novel antifolate currently under evaluation in a pivotal Phase 2 (PROPEL) trial in patients with relapsed or refractory peripheral T-cell lymphoma. The PROPEL trial is being conducted under an agreement reached with the U.S. Food and Drug Administration under its special protocol assessment, or SPA process. The Company is also investigating pralatrexate in patients with non-small cell lung cancer, bladder cancer and a range of lymphoma sub-types. The Company's other product candidate is RH1, a targeted chemotherapeutic agent currently being evaluated in a Phase 1 trial in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). The Company currently retains exclusive worldwide rights to pralatrexate and RH1 for all indications. For additional information, please visit the Company's website at www.allos.com.
Columbia University Medical Center
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The Medical Center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.
NewYork-Presbyterian Hospital -- based in New York City -- is the nation's largest not-for-profit, non-sectarian hospital, with 2,242 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth in U.S.News & World Report's guide to "America's Best Hospitals," ranks first on New York magazine's "Best Hospitals" survey, has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital is ranked with among the lowest mortality rates for heart attack and heart failure in the country, according to a 2007 U.S. Department of Health and Human Services (HHS) report card. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.