Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Bosutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive bosutinib PO daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Philip A Thompson

This phase II trial studies how well bosutinib works in treating patients with chronic myeloid leukemia in chronic phase after frontline tyrosine kinase inhibitor (TKI) failure. Bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess the response rate within 24 weeks in patients in chronic phase receiving bosutinib with the starting dose of 300 mg per day, with potential escalation to 400 mg, 500 mg and 600 mg per day.

SECONDARY OBJECTIVES:

I. Safety of dosing schedule. II. Frequency of treatment interruptions and dose reductions. III. Determine the rate of BCR-ABL/ABL \< 10% at 3 months and \< 1% at 6 months on the international scale and the rate of complete cytogenetic response (CCyR) at 6 months after the start of treatment.

IV. Determine the cumulative rate of CCyR. V. Determine the rate of major molecular response, molecular response (MR)4, MR4.5 and complete molecular response.

VI. Determine long-term outcomes, including progression-free survival, event-free survival, and overall survival.

VIII. Investigate the correlation between ABL kinase domain mutations, if present at the time of enrollment, with outcome.

IX. Determine the rate of development and type of ABL kinase domain mutations during therapy with bosutinib.

OUTLINE:

Patients receive bosutinib orally (PO) daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 2 years, every 24 weeks for 2 years.

Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure

An Open-Label Phase II Dose Optimization Study of Bosutinib at a Starting Dose of 300 Mg Daily for Adult Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase Post Frontline TKI Failure

Response is defined as follows: 1) For patients who do not currently have a partial cytogenetic response (PCyR), achievement of major cytogenetic response is considered a response. 2) For patients who are currently in PCyR, achievement of CCyR is considered a response. The Simon's optimal two-stage design will be used for interim futility monitoring. Will be estimated along with the 95% credible interval.

Will be estimated along with the exact 95% confidence intervals. Molecular assessments are based on quantitative reverse transcriptase polymerase chain reaction for Bcr-Abl in peripheral blood. Molecular response is categorized as MMR (Bcr-Abl/Abl ratio of \</= 0.1% in the international scale), MR4 (Bcr-Abl/Abl \</= 0.01%), and MR4.5 (BCR-ABL/ABL \</=0.0032%).

Will be assessed using the international scale. Will be estimated along with the exact 95% confidence intervals.

Will be assessed by Kaplan-Meier methods. Cox proportional hazards regression models will be fit to assess the association between patient characteristics including survival outcome. Time from date of treatment start until date of death due to any cause or last Follow-up.

Time from date of treatment start until the date of first objective documentation of disease-relapse.

Will be assessed by Kaplan-Meier methods. Transformation-free survival is defined as the time from treatment initiation until either progression to AP/BP or death from any cause.

Will be summarized and its association with survival outcomes will be analyzed through landmark analyses. Cox proportional hazards regression models will be fit to assess the association between patient characteristics including ABL kinase domain mutation status.

National Cancer Institute (NCI)

Pfizer

M.D. Anderson Cancer Center

Patients receive bosutinib PO daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Bosutinib: Given PO

Laboratory Biomarker Analysis: Correlative studies

Treatment (Bosutinib)

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Philip Thompson, MD/Assistant Professor

Response Rate

Interruptions

Reductions

Number of Participants With Treatment Interruptions and Dose Reductions

Complete Molecular Response (CMR)

MR4.5

Major Molecular Response (MMR)

Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response

Rates of BCR-ABL/ABL <10%

Rates of BCR-ABL/ABL < 1%

Overall Survival

Event-free Survival

Transformation-free Survival

There were not any at the start of treatment so there were not any mutation status to follow. These were not done.

Change of ABL Kinase Domain Mutation Status

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure	NCT02906696	Blasts Under 15... Blasts Under 15... Blasts Under 30... Blasts Under 30... Chronic Phase C...	Bosutinib Laboratory Biom...	18 Years -	M.D. Anderson Cancer Center
Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure	NCT02906696	Blasts Under 15... Blasts Under 15... Blasts Under 30... Blasts Under 30... Chronic Phase C...	Bosutinib Laboratory Biom...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for blasts under 15 percent of bone marrow nucleated cells