The U.S. Food and Drug Administration (FDA) has granted accelerated approval to belinostat (Beleodaq), a histone deacetylase inhibitor, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma, a rare and fast-growing type of non-Hodgkin lymphoma (NHL).
“This is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval expands the number of treatment options available to patients with serious and life-threatening diseases.”
The FDA granted accelerated approval to pralatrexate (Folotyn) in 2009 for use in patients with relapsed or refractory peripheral T-cell lymphoma and romidepsin (Istodax) in 2011 for the treatment of peripheral T-cell lymphoma in patients who received at least one prior therapy.
The safety and effectiveness of belinostat was evaluated in a multicenter, single-arm clinical trial of 120 evaluable patients with relapsed or refractory peripheral T-cell lymphoma. The median age of patients was 64 years (range, 29–81), 52% of patients were male, and the median number of prior treatments was two (range, 1-8). Patients received intravenous belinostat at 1,000 mg/m2 once daily on days 1 to 5 of a 21-day cycle. All participants were treated with belinostat until their disease progressed or side effects became unacceptable.
Overall response rate, the primary trial endpoint was 25.8% (95% confidence interval = 18.3–34.6), with 10.8% of patients achieving complete response and 15.0% achieving partial response. The median response duration was 8.4 months (95% CI = 4.5–29.4)
The most common side effects seen in belinostat-treated participants were nausea, fatigue, pyrexia, anemia, and vomiting. Serious adverse events were reported in 47% of patients. The most common serious adverse reactions were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multiorgan 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 III trial to characterize the comparative efficacy and safety of belinostat in combination with CHOP vs CHOP alone. ■