Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma.

Abstract

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

• Authors: Mridula Krishnan, R Gregory Bociek, Michelle Fanale, Swaminathan P Iyer, Mary Jo Lechowicz, Philip J Bierman, James O Armitage, Matthew Lunning, Avyakta Kallam, Julie M Vose
• Journal: Annals of hematology (Ann Hematol) Vol. 101 Issue 2 Pg. 335-340 (Feb 2022) ISSN: 1432-0584 [Electronic] Germany
• PMID: 34668982 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: © 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Chemical References

• Antineoplastic Agents
• Oligopeptides
• carfilzomib

Topics

• Adult
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Female
• Humans
• Lymphoma, T-Cell, Peripheral (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Oligopeptides (administration & dosage, adverse effects, therapeutic use)
• Progression-Free Survival
• Treatment Outcome