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

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Philadelphia Chromosome Positive CML, Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Chronic Phase Chronic Myelogenous Leukemia

In brief

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.

Key facts

Study ID

NCT04258943

Run by

Children's Oncology Group

People needed

60

Starts

2020-07-06

Expected to finish

2028-07-01

Last updated by the study team

2025-09-18

Who can join

Age: 1 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Inclusion criteria Phase 1 (R/I patients only)
• Cytogenetic and molecular diagnosis of Philadelphia chromosome-positive CML[2] at either time of initial CML diagnosis or at time of study screening:
• Cytogenetics must be performed by chromosome banding analysis (CBA) of bone marrow cell metaphases, and requires at least 20 metaphases.
• Only if dividing marrow cells cannot be obtained, or if there is an insufficient number of metaphases, CBA can be substituted by interphase fluorescence in situ hybridization (I-FISH) of bone marrow or peripheral blood cells, using dual color dual fusion probes, that allow the detection of BCR-ABL+ nuclei; at least 200 nuclei should be counted.
• Qualitative RT-PCR should be performed on RNA extracted from freshly collected bone marrow or peripheral blood cells. It identifies the transcript type, either e14a2 or 13a2 (also known as b3a2 and b2a2), or much more rarely e19a2, or e1a2, indicating the BCRABL protein weight (P210, rarely P230 or P190).
• 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).
• Intolerance to prior TKI therapy will be determined by the treating investigator, but generally applies to patients who are unable to receive standard or reduced doses of a TKI due to significant drug-related toxicity and/or when the drug-related toxicity is not responding to appropriate medical management. Patients who enroll as a result of intolerance to prior TKI therapy may have any level of response to their prior therapy and still be eligible.
• 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:
• For second-line and third-line CP CML patients:
• Absolute neutrophil count >1000/mm3 (>1.0 x109/L); Platelets ≥75,000/mm3 (≥75 x109/L) without any platelet transfusions during the preceding 7 days.
• For fourth-line CP and all for all AP/BP CML patients:
• Absolute neutrophil count >500/mm3 (>0.5 x109/L); Platelets ≥50,000/mm3 (≥50 x109/L) without any platelet transfusions during the preceding 7 days.
• 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:
• AST/ALT ≤2.5 x upper limit normal (ULN) or ≤5 x ULN if attributable to disease involvement of the liver; Total bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome.
• 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.
• Able to reliably swallow whole capsules, whole tablets; or drug added to a suitable foodstuff (from capsule contents, added to either apple sauce or yoghurt); or tablets and/or capsules dissolved in water as an oral syringe drinking solution, or tablets dissolved and administered by NG tube when needed.
• Serum/urine pregnancy test (for all girls ≥ age of menarche) negative at screening.
• Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active.
• Written informed consent of parent(s)/legal guardian(s) and/or patients (when applicable depending on age and local law and regulations)
• Patients (including legally acceptable representative for minors where applicable) who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Exclusion criteria Phase 1 (R/I patients only)
• Patients presenting with any of the following will not be included in the study:

Where it is running

• Phoenix Childrens Hospital — Phoenix, Arizona, United States
• Arkansas Children's Hospital — Little Rock, Arkansas, United States
• Kaiser Permanente Downey Medical Center — Downey, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Kaiser Permanene-Oakland — Oakland, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
• Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
• University of Florida Health Science Center - Gainesville — Gainesville, Florida, United States
• Nemours Children's Hospital — Orlando, Florida, United States
• Kapiolani Medical Center for Women and Children — Honolulu, Hawaii, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• Blank Children's Hospital — Des Moines, Iowa, United States
• Norton Children's Hospital — Louisville, Kentucky, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana-Farber/Harvard Cancer Center — Boston, Massachusetts, United States
• Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
• Children's Specialty Center of Nevada II — Las Vegas, Nevada, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Morristown Medical Center — Morristown, New Jersey, United States
• Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital — New Brunswick, New Jersey, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• The Steven and Alexandra Cohen Children's Medical Center of New York — New Hyde Park, New York, United States
• Children's Hospital of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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