Blasts Under 15 Percent of Bone Marrow Nucleated CellsPhase 2NCT02906696
Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure
A Phase 2 study testing Bosutinib and Laboratory Biomarker Analysis in people with Blasts Under 15 Percent of Bone Marrow Nucleated Cells and Blasts Under 15 Percent of Peripheral Blood White Cells, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- What is being tested?
- Bosutinib and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2016to 8 Aug 2019
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with chronic myeloid leukemia (CML) in chronic phase who have resistance and/or intolerance to frontline TKI therapy; resistance is defined as lack (lack defined as response not achieved or lost by the given dates mentioned hereafter) of CHR (complete hematologic response) within 3 months, lack of major cytogenetic response (MCyR) within 6 months, and lack of CCyR within 12 months of therapy with frontline TKIs; in addition, loss of MCyR, CCyR or MMR at any time during the course of therapy is also considered resistance to therapy; intolerance is defined as persistent or severe toxicity that is unacceptable to the patient
- Chronic phase disease is defined as:
- < 15% blasts in peripheral blood and bone marrow;
- < 30% blasts plus promyelocytes in peripheral blood and bone marrow;
- < 20% basophils in peripheral blood;
- >= 100 x 10^9/L platelets (>= 100,000/mm^3);
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- No evidence of extramedullary disease except hepatosplenomegaly; and
- No prior diagnosis of accelerated phase (AP) or blastic phase-chronic myeloid leukemia (BP-CML); patients with clonal evolution but no other criteria for accelerated phase are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Creatinine less than or equal to 2.0 mg/dl
- Bilirubin less than or equal to 2.0 mg/dl
- Alanine aminotransferase (ALT) less than or equal to 3 times institutional upper limit of normal
- Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include:
- Birth control pills, shots or implants (placed under the skin by a health care provider) or patches (placed on the skin);
- Intrauterine devices (IUDs);
- Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
- Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
- Patients or their legally authorized representative must provide written informed consent
Who cannot join
- Women who are pregnant or lactating
- Known to be human immunodeficiency virus (HIV)+
- Active and uncontrolled disease/infection that in the opinion of the treating physician and principal investigator may affect the ability to participate in the trial or put the patient at unduly high risk
- Unable or unwilling to sign the informed consent document
- Received no other investigational therapy within the past 14 days
- Presence of T315I mutation by ABL1 sequencing
- Patient is currently in complete cytogenetic remission (CCyR)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- 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
- Being tested
- Bosutinib, Laboratory Biomarker Analysis
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosutinibDrug
Also called Bosulif, SKI 606, SKI-606
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bosutinib) | Experimental | 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. Receives: Drug: Bosutinib; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
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.
Measured: Up to 6 months
Secondary outcomes (8)
Number of Participants With Treatment Interruptions and Dose Reductions
Will be summarized.
Measured: Up to 2 years
Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response
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%).
Measured: Up to 2 years
Rates of BCR-ABL/ABL <10%
Will be assessed using the international scale. Will be estimated along with the exact 95% confidence intervals.
Measured: At 3 months
Rates of BCR-ABL/ABL < 1%
Will be assessed using the international scale. Will be estimated along with the exact 95% confidence intervals.
Measured: At 6 months
Overall Survival
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.
Measured: Up to 2 years
Event-free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Measured: Up to 2 years
Transformation-free Survival
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.
Measured: Up to 2 years
Change of ABL Kinase Domain Mutation Status
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.
Measured: Baseline up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2016 (estimated)
- Study start28 Oct 2016
- Primary completion8 Aug 2019
- Study completion8 Aug 2019
Why it stopped: Terminated per PI's request due to competing priorities.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Blasts Under 15 Percent of Bone Marrow Nucleated CellsStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Pfizer
- Responsible party
- Sponsor
- Investigators
- Philip A Thompson, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02906696
- Sponsor's protocol ID
- 2016-0081
- Other IDs
- NCI-2016-01954, 2016-0081, P30CA016672
- Status last verified
- Apr 2020
- First submitted
- 15 Sep 2016
- Last updated
- 11 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No