Hodgkin Lymphoma Following Autologous Stem Cell Transplantation

A Randomized, Double-Blind, Placebo-Controlled Phase III Study of SGN-35 (brentuximab vedotin) and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Patients at High Risk of Residual Hodgkin Lymphoma (HL) Following Autologous Stem Cell Transplantation (ASCT) (The AETHERA Trial)

Seattle Genetics, Inc.

NCT01100502

This is an international trial with a goal accrual of 322 patients (~161 patients randomized per treatment arm) with approximately 50 trial sites in the United States, Europe, and the Russian Federation.

Eligibility criteria include patients ≥ 18 years of age with ECOG performance status of 0 or 1 and with high-risk classical HL who have received ASCT in the previous 30 to 45 days. Patients at high risk of residual HL post-ASCT are defined as follows: 1) a history of refractory HL (defined as patients progressing on or failing to achieve a complete remission following frontline standard chemotherapy or a combined modality therapy); 2) relapsed or progressive HL that occurs < 12 months from the end of frontline standard chemotherapy or combined modality treatment; and 3) extranodal involvement at time of pre-ASCT relapse. Patients are randomized in a 1:1 manner to receive SGN-35 1.8 mg/kg or placebo administered via outpatient IV infusion on day 1 of each 21-day cycle for a maximum of 16 cycles. The primary objective is to compare the progression-free survival of SGN-35 and BSC versus placebo and BSC. Secondary study objectives include comparison of overall survival between the two treatment arms, evaluation of the safety and tolerability of SGN-35 compared to placebo, and characterization of the incidence of anti-therapeutic antibodies.

HL and anaplastic large-cell lymphoma commonly express the CD30 antigen. SGN-35 is an anti-CD30 antibody conjugated to the anti-tubulin agent monomethyl auristatin E [MMAE] in order to enhance its anti-tumor activity. In a phase I, single-arm, open-label, dose-escalation study of SGN-35 in which the study population consisted primarily of patients with refractory/relapsed HL (including 73% with prior ASCT), the maximum tolerated dose was 1.8 mg/kg administered every three weeks. Tumor regression was observed in 36/42 (86%) evaluable patients, including 11 complete remissions (Younes A et al. New Engl J Med. 2010;363:1812-1821).

The five-year event-free survival rates for HL patients with intermediate- or high-risk disease is less than 30 percent post-ASCT, with the majority of relapses occurring within the first two years. Currently, there is no standard of care for HL patients who have received ASCT and are at high risk for disease relapse. Such patients may benefit from an agent that targets CD30 expressed on Reed–Sternberg cells. A similar strategy has been used in patients with relapsed/refractory follicular lymphoma where addition of rituximab maintenance after chemotherapy resulted in better overall survival than in patients who did not receive the antibody (Vidal L et al. J Natl Cancer Inst. 2009;101:248-255).