Pioglitazone Hydrochloride and Tyrosine Kinase Inhibitor in Treating Patients with Relapsed Chronic Myeloid Leukemia

Inclusion Criteria

• CML in any phase
• Philadelphia chromosome positive acute lymphoblastic leukemia
• Loss of 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
• 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
• 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
• 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 enrolment
• Chronic graft-versus-host disease requiring systemic immunosuppression post-allogeneic hematopoietic stem cell transplantation
• Cardiovascular disease: history of congestive heart failure, myocardial infarction within the 6 months of 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 PIO
• 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