Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin's lymphoma.

Abstract

This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in 67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).

• Authors: Vincent Ribrag, Dolores Caballero, Christophe Fermé, Emanuele Zucca, Reyes Arranz, Javier Briones, Christian Gisselbrecht, Gilles Salles, Alessandro M Gianni, Henry Gomez, Carmen Kahatt, Claudia Corrado, Sergio Szyldergemajn, Sonia Extremera, Bernardo de Miguel, Martin Cullell-Young, Franco Cavalli
• Journal: Haematologica (Haematologica) Vol. 98 Issue 3 Pg. 357-63 (Mar 2013) ISSN: 1592-8721 [Electronic] Italy
• PMID: 23065525 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• Peptides, Cyclic
• plitidepsin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacology, therapeutic use)
• Depsipeptides (pharmacology, therapeutic use)
• Female
• Humans
• Lymphoma, Non-Hodgkin (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Peptides, Cyclic
• Recurrence
• Treatment Outcome
• Tumor Burden (drug effects)
• Young Adult