On July 3, 2014, the U. S. Food and Drug Administration granted accelerated approval to belinostat (BELEODAQ, Spectrum Pharmaceuticals, Inc.) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
The approval was based on the results of a multi-center, single-arm trial of 120 evaluable patients with PTCL that was refractory or had relapsed after prior treatment and included patients with baseline platelets <100,000/microliters. The median age of the efficacy patient population was 64 years (range, 29-81), 52% of patients were male, and the median number of prior treatments was 2 (range, 1-8). Belinostat was administered by intravenous infusion at a dose of 1,000 mg/m2 once daily on days 1-5 of a 21-day cycle.
The primary trial endpoint was overall response rate (ORR) as assessed by an independent review committee. The ORR was 25.8% (95% CI: 18.3, 34.6). The overall complete and partial response rates were 10.8% and 15.0%, respectively. The median response duration (first date of response to disease progression or death) was 8.4 months (95% CI: 4.5-29.4).
The most common adverse reactions (>25%) in the safety population (N=129) were nausea, fatigue, pyrexia, anemia, and vomiting. Thrombocytopenia was reported in 16% of patients with grade 3 or 4 thrombocytopenia in 7% of patients. Serious adverse reactions were reported in 47% of patients. The most common serious adverse reactions (>2%) were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multi-organ failure. One treatment-related death due to hepatic failure was reported.
As a condition of this accelerated approval, FDA requires the sponsor to conduct a dose-finding trial of belinostat when combined with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) and a subsequent phase 3 trial to characterize the comparative efficacy and safety of belinostat in combination with CHOP versus CHOP alone.
The recommended dose and schedule for belinostat is 1,000 mg/m2 administered over 30 minutes by intravenous infusion once daily on days 1-5 every 3 weeks.
Full prescribing information is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).