NCT04258943

Bosutinib in Pediatric Patients With Newly Diagnosed Chronic Phase or Resistant/Intolerant Ph + Chronic Myeloid Leukemia

A Phase I/II Study of Bosutinib in Pediatric Patients With Newly Diagnosed Chronic Phase or Resistant/Intolerant Ph + Chronic Myeloid Leukemia", Study ITCC-054/COG-AAML1921

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 1 Year – 17 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1-2, multicenter, international, single-arm, open-label study designed to identify a recommended dose of bosutinib administered orally once daily in pediatric patients with newly diagnosed chronic phase Ph+ CML (ND CML) and pediatric patients with Ph+CML who have received at least one prior TKI therapy (R/I CML), to preliminary estimate the safety and tolerability and efficacy, and to evaluate the PK of bosutinib in this patient population.

Detailed description

The Phase 1 part of the study employs a 6+4 design (no DLT in 6 patients or 1 DLT in 10 patients) and incorporates additional PK information before escalating to the next dose level. If there is unacceptable toxicity or if PK results have exceeded the acceptable exposure levels for the adult equivalent dose, further dose escalation will be prohibited. The Recommended Phase 2 Dose (RP2D) is defined as the dose that results in equivalent(approximately ±20% of the adult values) PK exposure to 500 mg/day in adults and with 0 of 6 or \<2 DLTs observed out of 10 evaluable patients with Ph+ CML and resistance or intolerance to prior TKI therapy. The phase 2 part of the study will enroll the following patient populations. * Newly diagnosed (ND): newly diagnosed pediatric Ph + CML patients in chronic phase (CP) * Resistant/intolerant (R/I): chronic phase or advanced (accelerated (AP) or blast phase (BP) pediatric Ph+ CML patients with resistance or intolerance to at least 1 prior TKI

Conditions

• Philadelphia Chromosome Positive CML
• Accelerated Phase Chronic Myelogenous Leukemia
• Blastic Phase Chronic Myelogenous Leukemia
• Chronic Phase Chronic Myelogenous Leukemia

Interventions

Type	Name	Description
DRUG	Bosutinib	Patients with R/I disease are enrolled at a dose of 400 mg/m2 (DL2B) based on tolerability and PK analysis. Once the RP2D for R/I patients (RP2DR/I) is determined in the Phase 1, subsequent patients with R/I disease will be enrolled at the RP2DR/I for this subpopulation for the Phase 2 component of the study (see section 1.6.3 and section 3 for details). \- Patients with newly diagnosed disease are being enrolled on Phase 2 component only, at RP2DND dose of 300 mg/m2. (see section 1.6.3 and section 3 for details)

Timeline

• Start date: 2020-07-06
• Primary completion: 2028-07-01
• Completion: 2028-07-01
• First posted: 2020-02-06
• Last updated: 2025-09-18

Locations

59 sites across 8 countries: United States, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom

Regulatory

• FDA-regulated drug study