Bosutinib for Chronic Myeloid Leukemia

Not currently recruiting at 59 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral medication called bosutinib for children with chronic myeloid leukemia (CML). The goal is to determine a safe and effective dose for children who are newly diagnosed or have not responded to other treatments. Suitable candidates for this trial include children diagnosed with Philadelphia chromosome-positive CML who can swallow pills. As a Phase 1/Phase 2 trial, it aims to understand how the treatment works and measure its effectiveness in an initial group, offering participants early access to potentially beneficial therapy.

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.

Is there any evidence suggesting that bosutinib is likely to be safe for humans?

Research has shown that bosutinib is generally well-tolerated by people with chronic myeloid leukemia (CML). Studies have found it effective and safe for patients who did not respond well to other treatments like imatinib. Most patients experience manageable side effects.

The FDA has already approved bosutinib for treating both adults and children with a specific type of CML, indicating that its safety has been well-studied. While side effects are possible, existing research supports the treatment's overall safety for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bosutinib is unique because it offers a targeted approach for treating chronic myeloid leukemia (CML), focusing specifically on the BCR-ABL protein, which is often abnormal in CML patients. Unlike some standard treatments that might have broader effects, bosutinib zeroes in on this protein, potentially reducing side effects and improving efficacy. Researchers are excited about bosutinib because it has shown promise in overcoming resistance to other tyrosine kinase inhibitors (TKIs), which are common treatments for CML. Its oral administration makes it user-friendly, especially for pediatric patients, enhancing compliance and quality of life.

What evidence suggests that bosutinib might be an effective treatment for chronic myeloid leukemia?

Studies have shown that bosutinib, the treatment tested in this trial, effectively treats chronic myeloid leukemia (CML). Specifically, 86% of patients achieved complete remission, with no signs of the disease. About 53% experienced a major reduction in cancerous cells. Among those who took bosutinib long-term, more than half maintained their positive response for over ten years. These findings suggest bosutinib could be a strong option for managing CML. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4916618/

Safety and efficacy of bosutinib (SKI-606) in chronic phase ...

After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a major cytogenetic response (41% had a complete ...

2.

nature.com

nature.com/articles/s41375-024-02372-x

Efficacy and safety of bosutinib in previously treated ...

At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8–92.6); there were 17 deaths, including 2 that were considered CML ...

3.

bosulif.pfizerpro.com

bosulif.pfizerpro.com/efficacy/study-200-study-design

Study 200 Study Design

In a single-arm study of adults with CML who were resistant or intolerant to prior therapy, cardiac failure was observed in 5.3% of patients and cardiac ...

4.

clinical-lymphoma-myeloma-leukemia.com

clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)00022-3/fulltext

A Review of the Therapeutic Role of Bosutinib in Chronic ...

In addition, the probability of maintaining CCyR and MMR was over 58% and 56%, respectively, after ≥10 years. These long-term results ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2152265024000223

A Review of the Therapeutic Role of Bosutinib in Chronic ...

Several prospective trials have demonstrated the efficacy and acceptable safety profile of bosutinib as second-line therapy for patients with CP CML resistant ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2023/217729s000lbl.pdf

BOSULIF® (bosutinib) - accessdata.fda.gov

BOSULIF is indicated for the treatment of: • Adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive.

7.

ashpublications.org

ashpublications.org/blood/article/118/17/4567/29063/Safety-and-efficacy-of-bosutinib-SKI-606-in

Safety and efficacy of bosutinib (SKI-606) in chronic phase ...

These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4173127/

Bosutinib efficacy and safety in chronic phase chronic myeloid ...

Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up