We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

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

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Bosutinib
Given PO
Other Names:
  • Bosulif
  • SKI 606
  • SKI-606

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of Participants With Treatment Interruptions and Dose Reductions [ Time Frame: Up to 2 years ]
    Will be summarized.

  2. 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%).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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);
    • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Pfizer
Investigators
Layout table for investigator information
Principal Investigator: Philip A Thompson M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02906696    
Other Study ID Numbers: 2016-0081
NCI-2016-01954 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0081 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2016    Key Record Dates
Results First Posted: April 22, 2020
Last Update Posted: May 11, 2020
Last Verified: April 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases