Bosutinib for Chronic Myeloid Leukemia

Recruiting at 44 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Oncology Group

Must be taking: Tyrosine kinase inhibitors

Must not be taking: CYP3A4 inhibitors, Proton pump inhibitors

Disqualifiers: Acute lymphoblastic leukemia, Cardiac disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 6 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial requires that you stop using strong or moderate CYP3A4 inhibitors and inducers, proton pump inhibitors, and any prior TKI treatment within 7 days before starting bosutinib. Other anti-tumor or anti-leukemia treatments, except hydroxyurea and anagrelide, should be stopped 14 days before starting bosutinib.

What data supports the effectiveness of the drug bosutinib for treating chronic myeloid leukemia?

Bosutinib has been shown to be effective in treating chronic myeloid leukemia, especially in patients who are resistant or intolerant to other treatments. In a large trial, about one-third of patients who had not responded to previous treatments achieved a significant reduction in cancer cells after 24 weeks of taking bosutinib. ^{1 2 3 4 5}

Is bosutinib safe for treating chronic myeloid leukemia?

Bosutinib is generally safe for treating chronic myeloid leukemia, but it can cause side effects like diarrhea and liver issues. These side effects are usually manageable with proper care and medication. ^{1 2 6 7 8}

How is the drug Bosutinib unique in treating chronic myeloid leukemia?

Bosutinib is unique because it is an oral drug specifically used for patients with chronic myeloid leukemia who have not responded well to other treatments like imatinib, dasatinib, or nilotinib. It works by targeting specific proteins (BCR-ABL and SRC kinases) involved in cancer cell growth, and it is effective even in cases with certain mutations that make other drugs less effective. ^{2 3 5 9 10}

What is the purpose of this trial?

This trial tests bosutinib, a daily oral medication, in children with a type of leukemia. It aims to find a safe dose and see how well it works in those newly diagnosed or who haven't responded to other treatments. Bosutinib helps by blocking proteins that cancer cells need to grow. Bosutinib is a type of medication used for treating leukemia, especially in cases not responding to other treatments.

Eligibility Criteria

This trial is for pediatric patients aged 1-18 with newly diagnosed chronic phase Philadelphia chromosome-positive Chronic Myeloid Leukemia (Ph+ CML) or those resistant/intolerant to prior treatments. Participants must have proper bone marrow, kidney and liver function, not be pregnant, able to swallow medication whole, and willing to use effective contraception if applicable.

Inclusion Criteria

My kidneys are working well.

My leukemia is Philadelphia chromosome-positive.

I am not pregnant.

Exclusion Criteria

I have not taken any excluded medications recently.

Left ventricular ejection fraction <50% or shortening fraction <28%

I have been diagnosed with Ph+ acute lymphoblastic leukemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive bosutinib orally once daily in 28-day cycles

6 months

Cycle 1: Days 1, 8, 14, 22; Cycles 2-7: Start of every cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of treatment: within 28 days after last dose

Long-term Follow-up

Participants are monitored for long-term outcomes and survival

Up to 10 years

Treatment Details

Interventions

• Bosutinib

Trial Overview The study tests the drug Bosutinib in children with Ph+ CML. It's an open-label trial meaning everyone knows what treatment they're getting. The goal is to find a safe dose for kids who are either newly diagnosed or haven't responded well to previous therapies and see how their bodies handle the drug.

Participant Groups

Group I: Single Agent Bosutinib Experimental Treatment 1 Intervention

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). A treatment cycle is defined as 28 days

Bosutinib is already approved in United States for the following indications:

Approved in United States as Bosulif for:

• Treatment of adult patients with chronic, accelerated or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy
• Treatment of adult patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML)
• Treatment of pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML), newly-diagnosed or resistant or intolerant to prior therapy

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Erasmus Medical Center

Collaborator

Trials

742

Recruited

2,156,000+

Dutch Childhood Oncology Group

Collaborator

Trials

8

Recruited

4,500+

Innovative Therapies for Children with Cancer

Collaborator

Trials

1

Recruited

60+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Erasmus MC

Collaborator

Trials

2

Recruited

160+

Findings from Research

Bosutinib (Bosulif) received conditional marketing authorization in the EU for treating adult patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) who have previously been treated with other tyrosine kinase inhibitors and for whom standard treatments are not suitable.

The efficacy of bosutinib was primarily demonstrated in a subgroup analysis of a phase I/II study, focusing on patients with specific BCR-ABL mutations that indicate resistance to other treatments, highlighting its targeted mechanism of action as a kinase inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European medicines agency review of bosutinib for the treatment of adult patients with chronic myelogenous leukemia: summary of the scientific assessment of the committee for medicinal products for human use. Hanaizi, Z., Unkrig, C., Enzmann, H., et al.[2021]

Bosutinib is an effective treatment for chronic myeloid leukemia, particularly in patients who have developed resistance or intolerance to other tyrosine kinase inhibitors, demonstrating sustained efficacy in the chronic phase of the disease.

The safety profile of bosutinib includes distinct but manageable side effects, and it can be used without absolute contraindications in most patients, except those with specific mutations (T315I and V299L).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosutinib: a SRC-ABL tyrosine kinase inhibitor for treatment of chronic myeloid leukemia. Rassi, FE., Khoury, HJ.[2021]

Bosutinib is an effective second-generation tyrosine kinase inhibitor for treating chronic myeloid leukemia, showing efficacy in pivotal clinical trials with dosages of 400mg daily for first-line treatment and 500mg daily for later lines of treatment.

Management of bosutinib-related adverse events, particularly gastrointestinal symptoms and liver toxicity, is crucial for maintaining patient safety and treatment effectiveness, prompting expert recommendations for optimal management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimizing the use of bosutinib in patients with chronic-phase chronic myeloid leukemia: Recommendations of a panel of experts from the Fi-LMC (French CML working group)]. Rea, D., Cayssials, E., Charbonnier, A., et al.[2023]

In a phase III study involving 536 patients with newly diagnosed chronic-phase CML, bosutinib demonstrated significantly higher rates of major molecular response (47.2% vs. 36.9%) and complete cytogenetic response (77.2% vs. 66.4%) compared to imatinib after 12 months.

While bosutinib was more effective, it also had a higher incidence of gastrointestinal side effects and liver enzyme elevations, indicating a need for monitoring but suggesting it may be a strong first-line treatment option for CML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. Cortes, JE., Gambacorti-Passerini, C., Deininger, MW., et al.[2022]

In a phase I/II study involving 284 patients with chronic myeloid leukemia who had previously failed imatinib treatment, bosutinib showed durable efficacy, with 54% of patients remaining on treatment at 2 years and 40% at 5 years.

Bosutinib demonstrated a cumulative major cytogenetic response rate of 60% and a complete cytogenetic response rate of 50% by year 5, with manageable side effects primarily consisting of gastrointestinal issues, confirming its role as an effective second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Gambacorti-Passerini, C., Cortes, JE., Lipton, JH., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The European medicines agency review of bosutinib for the treatment of adult patients with chronic myelogenous leukemia: summary of the scientific assessment of the committee for medicinal products for human use. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Bosutinib: a review of its use in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. [2017]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I ascending single-dose study of the safety, tolerability, and pharmacokinetics of bosutinib (SKI-606) in healthy adult subjects. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Bosutinib: a SRC-ABL tyrosine kinase inhibitor for treatment of chronic myeloid leukemia. [2021]

6. France pubmed.ncbi.nlm.nih.gov

[Optimizing the use of bosutinib in patients with chronic-phase chronic myeloid leukemia: Recommendations of a panel of experts from the Fi-LMC (French CML working group)]. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Bosutinib in the management of chronic myelogenous leukemia. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia. [2022]

10. Italy pubmed.ncbi.nlm.nih.gov

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. [2019]