Peer-reviewed article
Phase 1/2 Study of Crizotinib in Children With Relapsed/Refractory ALK-Positive Anaplastic Large Cell Lymphoma or Neuroblastoma in Japan.
Mori T, Kada A, Osumi T, Tomizawa D, Koga Y et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a clinical trial of crizotinib, a cancer drug, in Japanese children with specific types of cancer (anaplastic large cell lymphoma and neuroblastoma). The study tested drug safety, dosage, and effectiveness in a small group of children. While the drug showed promise against the cancer, this is a specialized medical trial rather than research on child well-being more broadly.
Key points
Limitations
This document concerns a narrow medical intervention for rare childhood cancers and does not address child well-being, development, protection, or participation in the sense of the African Institute for Children Studies' framework.
Abstract
Clinical development of crizotinib in children with ALK-positive anaplastic large cell lymphoma (ALCL) was advanced in the US but not in Japan. The objectives of phase 1 part of a clinical study in Japan were to assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of crizotinib in children with relapsed/refractory (R/R) ALK-positive ALCL or neuroblastoma (NB). Two dose levels (165 and 280 mg/m2 twice daily (BID)) were planned to be evaluated. The aim of phase 2 part of the study was to assess the antitumor activity of crizotinib at the RP2D in children with R/R ALK-positive ALCL. Seven patients were eligible for phase 1 part, 5 with ALCL and 2 with NB. All 7 patients received crizotinib at a starting dose of 165 mg/m2 BID, with 1 dose-limiting toxicity observed (grade 3 gamma-glutamyltransferase increased). The most common grade 3 or 4 adverse event was neutropenia (71%). The steady-state Cmax and AUCtau of crizotinib at 165 mg/m2 BID were higher than expected. Considering the risk of a greater incidence of severe neutropenia, we decided that the 165 mg/m2 BID be the RP2D without evaluation at 280 mg/m2 BID. A total of 11 patients with ALK-positive ALCL were enrolled in the phase 2 part. The objective response rate was 72.7% (90% CI, 43.6%-92.1%). One patient permanently discontinued crizotinib due to disease progression. Crizotinib at 165 mg/m2 BID was well tolerated and showed favorable antitumor activity in children with R/R ALK-positive ALCL. Trial Registration: UMIN-CTR: UMIN000028075.