Bosutinib in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase After Frontline TKI Failure
Condition: 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
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
Intervention: Bosutinib; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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)