Positive Phase III Clinical Results With Humanized Antibody Therapy.(Brief Article)

2002 JAN 9 - (NewsRx.com & NewsRx.net) -- Protein Design Labs, Inc., (PDL) announced positive clinical results from the Phase III trial of its humanized antibody Zamyl (SMART M195) in patients with acute myeloid leukemia (AML).

The trial compared treatment with Zamyl plus a standardized chemotherapy regimen against treatment with chemotherapy alone in patients who had failed to achieve complete remission with initial therapy, or who had relapsed within one year of achieving complete remission. An initial review of the data by PDL indicates that Zamyl increased the overall response rate to 43% in the Zamyl plus chemotherapy patients (n=94) from 26% in the chemotherapy alone patients (n=97) (p=0.015), when all evaluable patients were analyzed on an intent-to-treat basis.

Certain subgroup analyses have also been performed, with a higher response rate seen in patients with longer initial complete remissions. For patients who had failed to achieve complete remission or had relapsed within six months of their first complete remission, the overall response rate was 32% in the Zamyl plus chemotherapy group (n=66), compared with 21% in the chemotherapy alone group (n=66) (p=0.237). However, for patients who had relapsed 7 to 12 months after their first complete remission, the overall response rate was 68% in the Zamyl plus chemotherapy group (n=28), significantly higher than the 35% overall response rate in the chemotherapy alone group (n=31) (p=0.019).

In this analysis, minimal requirements for an overall response were a bone marrow biopsy that demonstrated 5% or fewer blast cells and transfusion independence. The overall response category included patients who made a complete hematologic recovery as well as patients whose platelet counts were less than 100,000 per cubic millimeter. Patients were classified according to this definition without knowledge of their respective treatment assignments. This overall response criterion has been used in previous studies in acute myeloid leukemia evaluating the drug Mylotarg (gemtuzumab ozogamicin).

The data were also analyzed based upon a more stringent definition of complete response, which required complete hematological recovery, including a normal platelet and absolute neutrophil count and transfusion independence. This analysis showed a positive trend, with a complete response rate of 30% in the Zamyl plus chemotherapy arm compared with 21% in the chemotherapy alone arm (p=0.182) in the intent-to-treat analysis of all patients. A further analysis that required the complete response to occur within 70 days of the initiation of therapy, which was the prospectively defined primary endpoint of the trial, did not demonstrate statistically significant differences between the two arms of the trial.

Eric J. Feldman, MD, director of the Leukemia Program, Cornell University Medical Center - New York Presbyterian Hospital, and the lead investigator in the trial, presented the initial data December 7, 2001, during a PDL-sponsored corporate symposium at the 43rd Annual Meeting of the American Society of Hematology ...