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

NCT02782403 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 2015-0787NCI-2016-01188
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia (CML); Blast Phase Chronic Myelogenous Leukemia (CML); Chronic Phase Phase Chronic Myelogenous Leukemia (CML); Philadelphia Chromosome Positive (Ph+) Phase Chronic Myelogenous Leukemia (CML)

Outcome Measures

Primary Outcomes (3)

• 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)

  Up to 4 years

• 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)

  Up to 4 years

• 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)

  Up to 4 years

Secondary Outcomes (4)

• Clinical rates analysis (Chronic Phase Cohort)

  Up to 4 years

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

  Up to 4 years

• 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)

  Up to 4 years

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

  Baseline up to 4 years

Study Arms (2)

Treatment (alternating therapy)

EXPERIMENTAL

Patients 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.

Drug: Axitinib; Drug: Bosutinib; Other: Laboratory Biomarker Analysis

Treatment (combined therapy)

EXPERIMENTAL

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.

Drug: Axitinib; Drug: Bosutinib; Other: Laboratory Biomarker Analysis

Interventions

Axitinib DRUG

Given PO

Also known as: AG-013736, AG013736, Inlyta

Treatment (alternating therapy); Treatment (combined therapy)

Bosutinib DRUG

Given PO

Also known as: Bosulif, SKI 606, SKI-606

Treatment (alternating therapy); Treatment (combined therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alternating therapy); Treatment (combined therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase

Interventions

Axitinib; bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Prithviraj Bose

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study did not go on to the Phase II portion of the study due to low accrual and competing studies.

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: May 25, 2016
• Study Start: March 20, 2017
• Primary Completion: November 11, 2019
• Study Completion: November 11, 2019
• Last Updated: November 19, 2020

Record last verified: 2020-11

Locations

US (1)