The U. S. Food and Drug Administration has granted accelerated approval to belinostat for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The approval was based on the results of a multi-centre, 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, anaemia, 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 here.

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 an online form, or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Source: FDA