Phase 1b study to investigate the safety and tolerability of idelalisib in Japanese patients with relapsed/refractory follicular lymphoma and chronic lymphocytic leukemia.

Abstract

OBJECTIVE:

Idelalisib is an orally administered, highly selective inhibitor of phosphatidylinositol 3-kinase-δ. In this phase 1b study, the safety, tolerability and pharmacokinetics of idelalisib, an oral inhibitor of phosphatidylinositol 3-kinase-δ, were evaluated in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

METHODS:

In total, six patients (follicular lymphoma: n = 3, chronic lymphocytic leukemia: n = 3) were enrolled to receive idelalisib 150 mg twice daily.

RESULTS:

No dose-limiting toxicities were reported. The most common adverse events were diarrhea (n = 5), gastritis (n = 3), insomnia (n = 3) and pyrexia (n = 3). The most common ≥grade 3 adverse events were diarrhea (n = 2), increased transaminase levels (n = 2) and decreased appetite (n = 2). The maximum idelalisib plasma concentrations (Cmax) were achieved at 2.50 h (range: 1.50-4.00 h). The mean idelalisib plasma concentrations decreased over time but remained detectable in most patients at 12 h. All enrolled patients underwent efficacy evaluation by investigators, and five patients (follicular lymphoma: n = 2, chronic lymphocytic leukemia: n = 3) achieved partial response. The median duration of partial response was 14.5 months (range: 3.7-31.3 months).

CONCLUSION:

Idelalisib 150 mg twice daily was considered tolerable in Japanese patients with follicular lymphoma or chronic lymphocytic leukemia.(Clinical trial registration: NCT02242045).

• Authors: Noriko Fukuhara, Tomohiro Kinoshita, Kazuhito Yamamoto, Hirokazu Nagai, Koji Izutsu, Go Yamamoto, Pankaj Bhargava, Nishan Rajakumaraswamy, Rita Humeniuk, Anita Mathias, Guan Xing, Masato Fukui, Kensei Tobinai
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 50 Issue 12 Pg. 1395-1402 (Dec 16 2020) ISSN: 1465-3621 [Electronic] England
• PMID: 32856068 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antineoplastic Agents
• Purines
• Quinazolinones
• idelalisib

Topics

• Administration, Oral
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Humans
• Japan
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Lymphoma, Follicular (drug therapy, pathology)
• Male
• Middle Aged
• Purines (administration & dosage, adverse effects, pharmacokinetics)
• Quinazolinones (administration & dosage, adverse effects, pharmacokinetics)
• Recurrence
• Safety
• Treatment Outcome