Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure
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|ClinicalTrials.gov Identifier: NCT02906696|
Recruitment Status : Terminated (Terminated per PI's request due to competing priorities.)
First Posted : September 20, 2016
Results First Posted : April 22, 2020
Last Update Posted : May 11, 2020
|Condition or disease||Intervention/treatment||Phase|
|Blasts Under 15 Percent of Bone Marrow Nucleated Cells Blasts Under 15 Percent of Peripheral Blood White Cells Blasts Under 30 Percent of Bone Marrow Nucleated Cells Blasts Under 30 Percent of Peripheral Blood White Cells Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive||Drug: Bosutinib Other: Laboratory Biomarker Analysis||Phase 2|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||October 28, 2016|
|Actual Primary Completion Date :||August 8, 2019|
|Actual Study Completion Date :||August 8, 2019|
Experimental: Treatment (bosutinib)
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.
Other: Laboratory Biomarker Analysis
- Response Rate [ Time Frame: Up to 6 months ]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.
- Number of Participants With Treatment Interruptions and Dose Reductions [ Time Frame: Up to 2 years ]Will be summarized.
- Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response [ Time Frame: Up to 2 years ]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%).
- Rates of BCR-ABL/ABL <10% [ Time Frame: At 3 months ]Will be assessed using the international scale. Will be estimated along with the exact 95% confidence intervals.
- Rates of BCR-ABL/ABL < 1% [ Time Frame: At 6 months ]Will be assessed using the international scale. Will be estimated along with the exact 95% confidence intervals.
- Overall Survival [ Time Frame: Up to 2 years ]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.
- Event-free Survival [ Time Frame: Up to 2 years ]Time from date of treatment start until the date of first objective documentation of disease-relapse.
- Transformation-free Survival [ Time Frame: Up to 2 years ]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.
- Change of ABL Kinase Domain Mutation Status [ Time Frame: Baseline up to 2 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02906696
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Philip A Thompson||M.D. Anderson Cancer Center|