Active — Not RecruitingPhase 1/2

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

United States60 participantsStarted 2020-07-06

Plain-language 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.

Who can participate

Age range1 Year – 17 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Cytogenetic and molecular diagnosis of Philadelphia chromosome-positive CML\[2\] at either time of initial CML diagnosis or at time of study screening:
✓. Resistance (suboptimal response or failure, as defined by 2013 European Leukemia Net guidelines\[3\]) or intolerance (with or without suboptimal response or failure) to at least one prior tyrosine kinase inhibitor (TKI) The 2013 European LeukemiaNet guidelines\[3\] will be used to define suboptimal response and failure to prior TKI therapy. Details are provided in appendices 3 (intolerance or failure after one TKI) and 4 (Failure after more than one TKIs).
✓. Age ≥1 and \<18 years at day of attaining the informed consent.
✓. Lansky performance status ≥50% for patients ≤16 years of age, or Karnofsky scale ≥50% for patients \>16 years of age (appendix 5).
✓. Adequate bone marrow function:
✓. Adequate Renal Function: Subjects must have a calculated creatinine clearance (CrCl) ≥ 60mL/min/1.73 m2, using the Schwartz formula to estimate GFR (see appendix 11).
✓. Adequate liver function, including:
✓. Recovered to Grade 0-1, or to baseline, from any acute toxicities of prior chemotherapy, immunotherapy, radiotherapy, differentiation therapy, or biologic therapy, with the exception of alopecia.

What they're measuring

1. Incidence (and severity) of Dose-Limiting Toxicities (DLTs) assessed during the first 28 days of treatment.

Timeframe: First 28 days of treatment (first cycle)

PK parameters of bosutinib: Maximum observed plasma concentration (Cmax)

Timeframe: Cycle 1 Day 14: pre-dose & 1, 3, 6, 8, & 24 hours post-dose and before day 15 dosing; Cycles 2, 3 & 4, Day 1: 24 hours post Day 14 dose & before Day 15 dosing (each cycle is 28 days); unexpected and/or serious bosutinib-related AEs: when AE is detected

PK parameters of bosutinib:Time to Cmax (Tmax)

Timeframe: Cycle 1 Day 14: pre-dose & 1, 3, 6, 8, & 24 hours post-dose & before day 15 dosing; Cycles 2, 3 & 4, Day 1: 24 hours post Day 14 dose & before Day 15 dosing (each cycle is 28 days);for unexpected and/or serious bosutinib-related AEs: when AE is detected

PK parameters of bosutinib: Area under the plasma concentration versus time curve from time zero to the dosing interval (AUCτ)

PK parameters of bosutinib: Pre-dose concentration (Ctrough)

Trial details

NCT IDNCT04258943

SponsorChildren's Oncology Group

Sponsor typeNETWORK

Study typeINTERVENTIONAL

Primary completion2028-07

View on ClinicalTrials.gov More Philadelphia Chromosome Positive CML trials

Plain-language summary

Who can participate

Age range1 Year – 17 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Cytogenetic and molecular diagnosis of Philadelphia chromosome-positive CML\[2\] at either time of initial CML diagnosis or at time of study screening:
✓. Resistance (suboptimal response or failure, as defined by 2013 European Leukemia Net guidelines\[3\]) or intolerance (with or without suboptimal response or failure) to at least one prior tyrosine kinase inhibitor (TKI) The 2013 European LeukemiaNet guidelines\[3\] will be used to define suboptimal response and failure to prior TKI therapy. Details are provided in appendices 3 (intolerance or failure after one TKI) and 4 (Failure after more than one TKIs).
✓. Age ≥1 and \<18 years at day of attaining the informed consent.
✓. Lansky performance status ≥50% for patients ≤16 years of age, or Karnofsky scale ≥50% for patients \>16 years of age (appendix 5).
✓. Adequate bone marrow function:
✓. Adequate Renal Function: Subjects must have a calculated creatinine clearance (CrCl) ≥ 60mL/min/1.73 m2, using the Schwartz formula to estimate GFR (see appendix 11).
✓. Adequate liver function, including:
✓. Recovered to Grade 0-1, or to baseline, from any acute toxicities of prior chemotherapy, immunotherapy, radiotherapy, differentiation therapy, or biologic therapy, with the exception of alopecia.

What they're measuring

1. Incidence (and severity) of Dose-Limiting Toxicities (DLTs) assessed during the first 28 days of treatment.

Timeframe: First 28 days of treatment (first cycle)

PK parameters of bosutinib: Maximum observed plasma concentration (Cmax)

PK parameters of bosutinib:Time to Cmax (Tmax)

PK parameters of bosutinib: Area under the plasma concentration versus time curve from time zero to the dosing interval (AUCτ)

PK parameters of bosutinib: Pre-dose concentration (Ctrough)

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria