Trial Outcomes & Findings for Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure (NCT NCT02906696)

Last Updated: 2020-05-11

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2020-05-11

Participant Flow

Recruitment Period: October 2016 to November 2018

Participant milestones

Participant milestones
Measure	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. Bosutinib: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Bosutinib) n=8 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	44 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Response Rate	6 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Will be summarized.

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Number of Participants With Treatment Interruptions and Dose Reductions Interruptions	6 Participants
Number of Participants With Treatment Interruptions and Dose Reductions Reductions	4 Participants

SECONDARY outcome

Timeframe: 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%).

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response Complete Molecular Response (CMR)	2 Participants
Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response MR4.5	3 Participants
Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response MR4	3 Participants
Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response Major Molecular Response (MMR)	5 Participants

SECONDARY outcome

Timeframe: At 3 months

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

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Rates of BCR-ABL/ABL <10%	3 Participants

SECONDARY outcome

Timeframe: At 6 months

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

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Rates of BCR-ABL/ABL < 1%	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Overall Survival	20.26 Months Interval 13.63 to 22.9

SECONDARY outcome

Timeframe: Up to 2 years

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

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Event-free Survival	13.97 Months Interval 3.06 to 22.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Bosutinib) n=8 Participants 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
Transformation-free Survival	13.97 Months Interval 3.75 to 22.9

SECONDARY outcome

Timeframe: Baseline up to 2 years

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

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.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Bosutinib)

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Bosutinib) n=8 participants at risk 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
Cardiac disorders Chest Pain	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Diarrhea	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Gastrointestinal Bleed	12.5% 1/8 • Number of events 1 • up to 2 years
Injury, poisoning and procedural complications Arterial Rupture	12.5% 1/8 • Number of events 1 • up to 2 years
General disorders Viral Infection	12.5% 1/8 • Number of events 1 • up to 2 years

Other adverse events

Other adverse events
Measure	Treatment (Bosutinib) n=8 participants at risk 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
General disorders Abdominal Pain	25.0% 2/8 • Number of events 2 • up to 2 years
Investigations Elevated Alanine transaminase	50.0% 4/8 • Number of events 11 • up to 2 years
Blood and lymphatic system disorders Angioedema	12.5% 1/8 • Number of events 1 • up to 2 years
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 2/8 • Number of events 2 • up to 2 years
Investigations Aspartate transaminase	25.0% 2/8 • Number of events 4 • up to 2 years
Injury, poisoning and procedural complications Bruising	12.5% 1/8 • Number of events 1 • up to 2 years
General disorders Chest Pain	12.5% 1/8 • Number of events 1 • up to 2 years
Investigations Elevated Creatinine	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Diarrhea	87.5% 7/8 • Number of events 7 • up to 2 years
General disorders Fatigue	62.5% 5/8 • Number of events 5 • up to 2 years
General disorders Fever of Unknown origin	12.5% 1/8 • Number of events 1 • up to 2 years
Metabolism and nutrition disorders Hyperglycemia	12.5% 1/8 • Number of events 1 • up to 2 years
General disorders Headache	25.0% 2/8 • Number of events 2 • up to 2 years
Blood and lymphatic system disorders Anemia	25.0% 2/8 • Number of events 2 • up to 2 years
Reproductive system and breast disorders Irregular Menstration	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Mucositis	12.5% 1/8 • Number of events 1 • up to 2 years
Metabolism and nutrition disorders Sodium	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • up to 2 years
Nervous system disorders Sensory Neuropathy	12.5% 1/8 • Number of events 1 • up to 2 years
Eye disorders Periorbital Edema	12.5% 1/8 • Number of events 1 • up to 2 years
Skin and subcutaneous tissue disorders Pruritis	12.5% 1/8 • Number of events 1 • up to 2 years
Skin and subcutaneous tissue disorders Rash	37.5% 3/8 • Number of events 3 • up to 2 years
Infections and infestations Upper Respiratory Infection	12.5% 1/8 • Number of events 1 • up to 2 years
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • up to 2 years
Infections and infestations Yeast Infection	12.5% 1/8 • Number of events 1 • up to 2 years

Additional Information

Philip Thompson, MD/Assistant Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-792-7430

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place