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Accelerated Phase Chronic Myelogenous Leukemia (CML)Phase 1NCT02782403

Axitinib and Bosutinib in Treating Patients With Chronic, Accelerated, or Blastic Phase Chronic Myeloid Leukemia

A Phase 1 study testing Axitinib, Bosutinib and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia (CML) and Blast Phase Chronic Myelogenous Leukemia (CML), run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of axitinib and bosutinib and how well they work in treating patients with chronic, accelerated, or blastic phase chronic myeloid leukemia. Axitinib and 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
What is being tested?
Axitinib, Bosutinib and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
20 Mar 2017to 11 Nov 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Diagnosis of Philadelphia chromosome positive (Ph+) (by cytogenetics or FISH) or BCR-ABL+ (by polymerase chain reaction [PCR]) CML in CP (cohort 1), AP (cohort 2) or BP (cohort 2)
  • Patients should have failed (demonstrated resistance, intolerance or treatment discontinuation for any other reason of) at least 3 Food and Drug Administration (FDA)-approved TKIs if in CP (cohort 1), or at least 1 FDA-approved TKI if in AP (cohort 2); resistance will be defined as meeting the criteria for failure or warning by the European Leukemia Net (ELN); no prior therapy is necessary for patients in BP (cohort 2); patients in CP who have failed < 3 TKIs, but are ineligible to receive other FDA-approved TKIs, may also be enrolled in cohort 1; at least 10 CP patients with the T315I mutation affecting the kinase domain of Bcr-Abl will be enrolled in cohort 1, as well as in the phase II portion of cohort 2
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless due to Gilbert syndrome, in which case it should be =< 3.0 x ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
  • Serum creatinine =< 1.5 x ULN
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  • Patients must sign the Institutional Review Board (IRB)-approved informed consent document for this trial
  • Reliable telephone access so as to be able to receive calls from an interactive voice response (IVR) system (only applicable to patients participating in the optional symptom burden assessment portion)
  • Women of childbearing potential (WOCBP) must practice 2 effective methods of birth control during the course of the study; male patients who are partners of WOCBP should also practice an effective method of contraception: postmenopausal women must be amenorrheic for >= 12 months to be considered of non-childbearing potential; women and men must continue birth control for the duration of the trial and >= 3 months after the last dose of study drug; all WOCBP MUST have a negative pregnancy test prior to first receiving study medication(s)
  • Patients should have discontinued therapy with imatinib, dasatinib, nilotinib, ponatinib, omacetaxine or other anti-leukemia therapy (except hydroxyurea) >= 48 hours prior to start of study therapy and recovered from any toxicity due to these therapies to grade =< 1; hydroxyurea may be received up to the time of enrollment and for the first 6 weeks of study treatment if necessary

Who cannot join

  • Prior therapy with axitinib; prior therapy with bosutinib is allowed, except in the following circumstances: the subject is currently on bosutinib; bosutinib is the subject's most recent TKI for CML; the subject has a history of intolerance to bosutinib
  • Active gastrointestinal conditions that are expected to impair absorption of orally administered medications
  • Patients who currently have or have a history of the following within 6 months preceding study entry are not eligible: unstable angina (UA), myocardial infarction (MI), transient ischemic attack (TIA), stroke, deep vein thrombosis (DVT), acute peripheral or pulmonary arterial thromboembolism (PE); clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes); New York Heart Association class III or IV heart failure
  • Patients with active, uncontrolled psychiatric disorders including: psychosis, major depressive, and bipolar disorders
  • Patients with uncontrolled hypertension (defined as sustained systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg)
  • Pregnant or breast-feeding women are excluded
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  • Inability to understand a written informed consent document
  • Patients receiving anticoagulants that are unable to be discontinued
  • Patients with active, uncontrolled infection
  • Patients with a history of hypersensitivity to bosutinib or axitinib
  • Patients on proton pump inhibitors, potent CYP3A or P-glycoprotein substrates, inhibitors or inducers a minimum 7 day period washout required unless discontinuation or substitution is not in the best interests of the patient as determined by the investigator; in instances where use of these agents is felt to be required for optimal management, inclusion of such patients should be discussed with the principal investigator (PI) and the rationale documented; these patients, if enrolled on study, may require dose modifications for both axitinib and bosutinib

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Alternating or Combined Therapy With Axitinib and Bosutinib for Patients With Chronic Myeloid Leukemia in Chronic, Accelerated, or Blastic Phases

This phase I/II trial studies the side effects and best dose of axitinib and bosutinib and how well they work in treating patients with chronic, accelerated, or blastic phase chronic myeloid leukemia. Axitinib and bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the rate of major cytogenetic response (MCyR) of an alternating schedule of axitinib and bosutinib in patients with chronic myeloid leukemia, chronic phase (CML-CP) after failure of/intolerance to >= 3 tyrosine kinase inhibitors (TKIs) using standard response criteria. (Chronic Phase Cohort) II. To determine the recommended phase II doses (RPTDs) of axitinib and bosutinib in combination in patients with chronic myeloid leukemia (CML) in accelerated phase (CML-AP) or blast phase (CML-BP). (Advanced phase [AP] patients must have received >= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) III. To evaluate the rate of major hematologic response (MaHR) of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP using standard response criteria. (AP patients must have received >= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion)

SECONDARY OBJECTIVES:

  1. To determine the rate of complete cytogenetic response (CCyR), breast cancer gene (BCR-ABL/ABL) =< 10% and =< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points. (Chronic Phase Cohort) II. To determine the duration of response (DOR), event-free survival (EFS), transformation-free survival (TFS), failure-free survival (FFS) and overall survival (OS) for patients with CML-CP treated with alternating axitinib and bosutinib after failure of/intolerance to >= 3 TKIs. (Chronic Phase Cohort) III. To determine the safety and tolerability of alternating therapy with axitinib and bosutinib after failure of/intolerance to >= 3 TKIs. (Chronic Phase Cohort) IV. To establish the response rate of concurrent administration of axitinib and bosutinib to patients with CML-AP or CML-BP. (AP patients must have received >= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) V. To determine the rate of complete hematologic response (CHR), complete cytogenetic response (CCyR), BCR-ABL/ABL =< 10% and =< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP. (AP patients must have received >= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) VI. To determine the DOR, EFS, TFS, FFS and OS for patients with CML-AP or -BP treated with combined axitinib and bosutinib. (AP patients must have received >= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion) VII. To evaluate the probability of developing Abl kinase domain and other somatic mutations in patients with CML treated with alternating (CP) or concurrent (AP/BP) axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) VIII. To analyze differences in response rates, duration and survival according to pre-treatment mutations and patient characteristics in both the CP and AP/BP cohorts. (Advanced Phase Cohort - Phase II Portion) IX. To characterize mechanisms of resistance in patients who develop resistance to alternating (CP) or concomitant (AP/BP) therapy with axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) X. To evaluate symptom burden in patients with CML receiving axitinib and bosutinib, whether alternating (CP) or in combination (AP/BP). (Advanced Phase Cohort - Phase II Portion)

OUTLINE: This is a dose-escalation followed by a phase II study. Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients with chronic phase CML receive either bosutinib orally (PO) once a day (QD) or axitinib PO twice a day (BID) alone for 3 months. Patients then switch to the other drug for 3 months and alternate between the two every 3 months in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients with accelerated or blastic phase CML receive bosutinib PO QD and axitinib PO BID for 3 months. Courses repeat every 3 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month.

Being tested
Axitinib, Bosutinib, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myeloid, Chronic-Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AxitinibDrug

    Also called AG-013736, AG013736, Inlyta

    Given PO

  • BosutinibDrug

    Also called Bosulif, SKI 606, SKI-606

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02782403
Study groupRoleWhat they receive
Treatment (alternating therapy)ExperimentalPatients with chronic phase CML receive either bosutinib PO QD or axitinib PO BID alone for 3 months. Patients then switch to the other drug for 3 months and alternate between the two every 3 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Axitinib; Drug: Bosutinib; Other: Laboratory Biomarker Analysis
Treatment (combined therapy)ExperimentalPatients with accelerated or blastic phase CML receive bosutinib PO QD and axitinib PO BID for 3 months. Courses repeat every 3 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Axitinib; Drug: Bosutinib; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of major cytogenetic response (MCyR) among patients with chronic myeloid leukemia, chronic phase status post (s/p) failure of/intolerance to >= 3 tyrosine kinase inhibitors treated with alternating axitinib and bosutinib (Chronic Phase Cohort)

    Measured: Up to 4 years

  2. Maximum tolerated doses of the combination of axitinib and bosutinib among patients with chronic myeloid leukemia (CML)-advanced phase (AP) or -blast phase (BP) (AP patients must have received >= 1 prior TKI) (Advanced phase cohort - Phase I Portion)

    Measured: Up to 4 years

  3. Complete hematologic response (CHR) rate to the combination of axitinib and bosutinib among patients with CML-AP or -BP (AP patients must have received >= 1 prior TKI) (Advanced phase cohort - Phase II Portion)

    Measured: Up to 4 years

Secondary outcomes (4)

  1. Clinical rates analysis (Chronic Phase Cohort)

    Rates of CHR, complete cytogenetic response (CCyR), major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), complete molecular response (CMR), BCR-ABL/ABL =< 10% and =< 1%, duration of response (DOR), event-free survival (EFS), transformation-free survival (TFS), failure-free survival (FFS) and overall survival (OS) among patients with CML-CP after resistance and/or intolerance to >= 2 TKIs treated with alternating axitinib and bosutinib.

    Measured: Up to 4 years

  2. Incidence and severity of adverse events (AEs) (Advanced phase cohort - Phase I Portion)

    Will be determined by history and physical examination and laboratory assessment, seen with the combination of axitinib and bosutinib among patients with CML-AP or -BP.

    Measured: Up to 4 years

  3. Rates of CHR, CCyR, MMR, MR4, MR4.5, CMR, BCR-ABL/ABL =< 10% and =< 1%, DOR, EFS, TFS, FFS and OS among patients with CML-AP or -BP receiving combined therapy with axitinib and bosutinib (Advanced phase cohort - Phase II Portion)

    Measured: Up to 4 years

  4. Percentage of participants with mutations in BCR-ABL and other genes in all patients receiving study drugs

    Measured by analysis of each patient's multigene profile using Next Generation Sequencing (NGS) panel and/or ABL kinase domain sequencing performed at baseline.

    Following the analysis of each patient's mutation profile, the number of each somatic mutation identified will be reported.

    Measured: Baseline up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2016 (estimated)
  2. Study start20 Mar 2017
  3. Primary completion11 Nov 2019
  4. Study completion11 Nov 2019

Why it stopped: Terminated per PI's request at the time of CR. Study was closed due to low/slow accrual due to other competing studies.

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This study did not go on to the Phase II portion of the study due to low accrual and competing studies.
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02782403
Sponsor's protocol ID
2015-0787
Other IDs
NCI-2016-01188, 2015-0787
Status last verified
Nov 2020
First submitted
20 May 2016
Last updated
19 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Axitinib, Bosutinib and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia (CML) and Blast Phase Chronic Myelogenous Leukemia (CML), run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Terminated per PI's request at the time of CR. Study was closed due to low/slow accrual due to other competing studies.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of major cytogenetic response (MCyR) among patients with chronic myeloid leukemia, chronic phase status post (s/p) failure of/intolerance to >= 3 tyrosine kinase inhibitors treated with alternating axitinib and bosutinib (Chronic Phase Cohort) (time frame: Up to 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02782403.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020; AzTrials last refreshed its copy on 7 Nov 2026.

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