This phase II/III trial studies how well eltrombopag olamine works in treating thrombocytopenia in patients with chronic myeloid leukemia or myelofibrosis receiving tyrosine kinase inhibitor therapy. Eltrombopag olamine may cause the body to make platelets after receiving treatment for chronic myeloid leukemia or myelofibrosis.

The goal of this clinical research study is learn if eltrombopag can help control or prevent low platelet counts in patients receiving treatment for CML or myelofibrosis. This is an investigational study. Eltrombopag is FDA approved and commercially available for the treatment of patients with low platelet counts. The use of eltrombopag for the treatment of low platelet counts in patients with CML and myelofibrosis is investigational. Eltrombopag will be provided at no cost to you during the study.

If you are found to be eligible to take part in this study, you will receive eltrombopag by mouth 1 time a day. Your dose may be increased every 2 weeks depending on your platelet count response. You should take eltrombopag on an empty stomach. You should not eat for 2 hours before taking eltrombopag. You should wait at least 4 hours between taking eltrombopag and taking other drugs (like antacids), dairy products, juices with calcium added, or supplements containing iron, calcium, aluminum, magnesium, selenium, or zinc.

Up to 39 patients will take part in this study. All will be enrolled at MD Anderson. As of June 6, 2017, the study is closed to new participants.

Inclusion Criteria:

• CML patients in chronic phase receiving treatment with any Food and Drug Administration (FDA) approved TKI; or CML patients in accelerated or blastic phase who are considered to be in this phase because of thrombocytopenia or because of clonal evolution and with no other criteria for accelerated/blastic phase or patients with myelofibrosis receiving treatment with FDA approved TKI and with peripheral blood and/or bone marrow blasts =< 10%
• Grade >= 3 thrombocytopenia (platelets < 50 x 10^9/L) after the first 3 months of therapy with the TKI for patients with CML and platelets < 100 x 10^9/L for patients with MF after the first 3 months of therapy; thrombocytopenia must be either recurrent (i.e., second or greater episode of thrombocytopenia) or having required dose reductions of the TKI
• Subject is anticipated to have therapy with TKI continued for >= 3 months
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for Gilbert's syndrome)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN
• Creatinine =< 2 x ULN

Exclusion Criteria:

• CML patients in accelerated or blastic phase except for those who are considered to be in this phase because of thrombocytopenia or because of clonal evolution and with no other criteria for accelerated/blastic phase; or myelofibrosis patients who have transformed to acute leukemia or have >= 10% blasts in peripheral blood and/or in bone marrow

• Thrombocytopenia that is considered to be unrelated to treatment with TKI or accelerated phase as defined above

• Stem cell transplantation within preceding 60 days prior to registration

• Patients with documented active hepatitis B or C infection

• Patients with known bone marrow reticulin fibrosis (>= grade 2) (only applicable to patients with CML)

• Patients with palpable splenomegaly >= 16 cm below coastal margin (only applicable to patients with CML)

• Female subjects who are pregnant or breastfeeding

• Women of childbearing potential are required to have a beta human chorionic gonadotropin (BHCG) serum or urine pregnancy test performed within 7 days prior to first study drug dose; a female of childbearing potential is a sexually mature woman who:

  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

• Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation

• Patients with known risk factors for thromboembolism (e.g. Factor V Leiden mutation, antithrombin III (ATIII) deficiency, Protein C and S deficiency, antiphospholipid syndrome, portal hypertension, etc.)