Pioglitazone and Tyrosine Kinase Inhibitor in Treating Patients With Relapsed Chronic Myeloid Leukemia
Condition: Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: Pioglitazone; Tyrosine Kinase Inhibitor (TKI)
Intervention description: Given PO; Given TKI therapy
Intervention MeSH terms: Pioglitazone; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pioglitazone hydrochloride and tyrosine kinase inhibitor
      (TKI) therapy works in treating patients with chronic myeloid leukemia (CML) that has come
      back after a period of improvement (relapsed) after a first TKI discontinuation. TKI may stop
      the growth of cancer cells by blocking certain enzymes need for cell growth. Although TKI
      therapies are effective against CML, there are residual cancer cells called leukemia stem
      cells that are able to hide from TKIs. Pioglitazone is a drug approved by the Food and Drug
      Administration to treat diabetes and has been shown in laboratory studies to increase CML
      stem cell death when given together with TKI therapy. Giving pioglitazone with TKI therapy
      may be effective in treating patients with CML.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic myeloid leukemia (CML) in any phase

          -  Philadelphia chromosome positive acute lymphoblastic leukemia

          -  Loss of major molecular response (MMR) following a first TKI discontinuation trial

          -  Serum bilirubin < 1.5 x upper limit of normal values

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2.5 x upper limit of normal values

          -  Females of child bearing potential must agree to abstain from sexual activity or to
             use a medically approved contraceptive measure/regimen during and for 3 months after
             the treatment period; women of child bearing potential must have a negative urine
             pregnancy test at the time of enrollment; acceptable methods of birth control include
             oral contraceptive, intrauterine device, transdermal/implanted or injected
             contraceptives and abstinence

          -  Males must agree to abstain from sexual activity or agree to utilize a
             medically-approved contraception method during and for 3 months after the treatment
             period

          -  Patient requiring anti-diabetic medications to manage hyperglycemia are eligible.
             Adjustments of other anti-diabetic agents will be made with close monitoring of blood
             glucose

          -  Informed consent

          -  Be able and willing to comply with study visits and procedures

        Exclusion Criteria:

          -  Known loss of complete cytogenetic response (CCyR) by marrow cytogenetic or blood
             fluorescence in situ hybridization (FISH) for breakpoint cluster region (BCR)- v-abl
             Abelson murine leukemia viral oncogene homolog 1 (ABL1)

          -  Loss of complete hematologic response (CHR)

          -  Participation in another clinical trial with any investigative drug within 30 days
             prior to study enrollment

          -  Chronic graft-versus-host disease requiring systemic immunosuppression post-allogeneic
             hematopoietic stem cell transplantation

          -  Cardiovascular disease: history of congestive heart failure, myocardial infarction in
             the 6 months preceding study entry, symptomatic cardiac arrhythmia requiring treatment

          -  History of bladder cancer

          -  Gross (visible) hematuria

          -  Known history of osteoporosis

          -  Known history of macular edema

          -  Known history of ABL1-domain mutation that predicts resistance to the discontinued TKI

          -  Significant medical or psychiatric disorder that would interfere with consent, study
             participation, or follow-up

          -  Known allergy to pioglitazone

          -  Pregnant or breastfeeding

          -  Use of thiazolidinedione (TZD) within 28 days prior to enrollment

          -  Significant gastrointestinal condition that could potentially impair the absorption or
             disposition of the drug

          -  Uncontrolled peripheral edema (2+ or more) of any etiology

          -  Active cancer that requires therapy in the form of chemotherapy or radiation