Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

Abstract

UNLABELLED:

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL.

CLINICAL TRIAL REGISTRATION:

NCT01704963.

• Authors: Kensei Tobinai, Michinori Ogura, Kenichi Ishizawa, Tatsuya Suzuki, Wataru Munakata, Toshiki Uchida, Tomohiro Aoki, Takanobu Morishita, Yoko Ushijima, Satoko Takahara
• Journal: International journal of hematology (Int J Hematol) Vol. 103 Issue 1 Pg. 86-94 (Jan 2016) ISSN: 1865-3774 [Electronic] Japan
• PMID: 26588924 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Piperidines
• Pyrazoles
• Pyrimidines
• ibrutinib
• Protein-Tyrosine Kinases
• Agammaglobulinaemia Tyrosine Kinase
• BTK protein, human
• Adenine

Topics

• Adenine (analogs & derivatives)
• Adult
• Agammaglobulinaemia Tyrosine Kinase
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Asian People
• Enzyme Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Female
• Humans
• Lymphoma, B-Cell (drug therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Piperidines
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Pyrazoles (administration & dosage, adverse effects, pharmacokinetics)
• Pyrimidines (administration & dosage, adverse effects, pharmacokinetics)
• Recurrence
• Treatment Outcome