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Final results of a pivotal Phase 2 clinical trial of pralatrexate (PDX) for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) were reported 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/Columbia. T-cell lymphoma (PTCL) is 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.

Data from the PROPEL (Pralatrexate in patients with Relapsed Or refractory Peripheral T-cell Lymphoma) trial show that pralatrexate, a drug that partially works by mimicking the vitamin folic acid, has an estimated median duration of response of 287 days, or 9.4 months. As previously reported, 29 of 109 evaluable patients, or 27 percent, showed a complete or partial response.

"Until now, these patients could only expect to survive several weeks. This study shows that it may be possible to extend this to many months — a result that is nothing short of spectacular and may likely represent a breakthrough in the development of new drugs for T-cell lymphoma," said Dr. 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/Columbia University Medical Center, and associate professor of medicine at Columbia University College of Physicians and Surgeons. "Based on these promising data, pralatrexate has the potential to play a clinically meaningful role in the treatment of patients with relapsed or refractory PTCL."

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.

There are currently no pharmaceutical agents approved for use in the treatment of either first-line or relapsed or refractory PTCL, and overall five-year survival is approximately 25 percent after first-line therapy. In addition to those PTCL patients who do not respond to first-line treatment, a significant number of first-line multi-agent chemotherapy responders relapse or become refractory after treatment.

The PROPEL trial is organized by Allos Therapeutics Inc., the maker of the drug. The company expects to submit a New Drug Application to the U.S. Food and Drug Administration for marketing approval of pralatrexate sometime in the first half of 2009. The results of the trial will be submitted for presentation at an upcoming scientific meeting and for publication in a peer-reviewed journal.

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.

PROPEL Trial Details

The critical PROPEL (Pralatrexate in patients with Relapsed Or refractory Peripheral T-cell Lymphoma) trial — an international, multicenter, open-label, single-arm study — enrolled a total of 115 patients with relapsed or refractory PTCL, 109 of whom are considered evaluable for response according to the trial protocol. It is believed that PROPEL is the largest prospectively designed single-agent trial conducted to date for this patient population.

To be eligible for the trial, patients' disease must have progressed after at least one prior treatment. Patients were considered evaluable if they received at least one dose of pralatrexate and their diagnosis of PTCL was confirmed by independent pathology review. 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. The primary endpoint of the trial is objective response rate, as assessed by central, independent oncology review using International Workshop Criteria (IWC). Duration of response is the key secondary endpoint.

Of the 29 patients who achieved a response according to central independent oncology review, 7 patients had a complete response (CR), 2 patients had a complete response unconfirmed (CRu) and 20 patients had a partial response (PR). According to the PROPEL investigators, 42 of 109 evaluable patients, or 39 percent, achieved a response. Of these, 15 patients had a CR, 4 patients had a CRu and 23 patients had a PR. PROPEL patients received a median of three prior systemic treatment regimens (range of 1 to 12), including 18 patients, or 16 percent, who had previously undergone an autologous stem cell transplant. In the trial, 66 percent of the patients who responded did so after cycle one of therapy. Patients will continue to be followed for long-term survival.

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 2009. Annual prevalence is estimated to be approximately 9,500 patients. In addition to the 30 percent 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.

For more information, patients may call 866-NYP-NEWS.

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Columbia University Medical Center

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