Final Results of a Phase 2 NCI Multicenter Study of Romidepsin in Patients with Relapsed Peripheral T-Cell Lymphoma (PTCL).

The histone deacetylase (HDAC) inhibitors are a class of epigenetic agents undergoing clinical testing. HDAC inhibitors modulate expression of genes involved in cell cycle regulation, leading to induction of differentiation or apoptosis. Romidepsin, a novel pan-HDAC inhibitor, has previously demonstrated activity as a single agent in patients (pts) with cutaneous T-cell lymphoma (CTCL) in two phase 2 studies.

To evaluate the efficacy and tolerability of romidepsin in the treatment of advanced PTCL and as an exploratory endpoint, to examine the molecular effects of romidepsin in both PTCL and CTCL.

This Phase 2, open-label, multi-arm, multicenter study enrolled 46 PTCL pts from the NCI and 9 extramural sites. CTCL pts were also enrolled in this study. This study is now closed to accrual. Pts with relapsed or refractory PTCL who had received at least one prior standard chemotherapy regimen were eligible. Pts received romidepsin 14 mg/m² as a 4-hr infusion on days 1, 8 and 15 every 28 days. Responses were assessed using elements of the IWG criteria and RECIST, as appropriate, for pts with lymph node involvement and extranodal disease.

46 pts (24 [52%] men and 22 [48%] women) with a mean age of 59 (range: 28 to 84) years were treated with romidepsin. 32 pts received ≥ 2 cycles of therapy. Mean number of prior therapies was 4.8 (range 1 to 14). Objective disease response rates (ORR) are summarized in the table. The mean number of cycles of treatment was 6.8 (range 1-47) and the overall median duration of response was 9.0 months (range 1.8 months to 5.8 yrs) for all pts. The median duration of response for the 5 pts who achieved CR was 6.0 months (range 2.8 months to 5.8 yrs).The most frequent drug-related AEs (all grades, all cycles) were generally mild and included: nausea (74%; 9% ≥grade 3), fatigue (72%; 20% ≥grade 3), decreased platelets (72%; 35% ≥grade 3), cardiovascular/general-other (72%; 0% ≥grade 3) and decreased AGC (65%; 43% ≥grade 3). One death, in a pt with significant cardiovascular disease who had achieved a CR, was considered possibly related to treatment.

Conclusions

This study demonstrates tolerability and durable clinical benefit (ORR of 33% and median duration of response of 9.0 months) of romidepsin in pts with recurrent or refractory PTCL. Based on these promising results, a Phase 2B protocol investigating romidepsin in pts with relapsed or refractory PTCL is ongoing at multiple international centers.

Kirschbaum:Gloucester Pharmaceuticals: Consultancy.