A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin

Inclusion Criteria

• Adult age between 18 years and 55 years
• Body mass index (BMI) greater than 18.5 kg/m^2
• At least 8 years formal education, with appropriate reading and comprehension skills
• Able and willing to provide written informed consent
• Males must agree to using contraception during the study and for 2 weeks after the last dose of study drug.
• If a female participant is of reproductive potential, the participant (and her partner) must agree to use of one of the following combinations of birth control during the study and for 2 weeks after the last dose of study drug (or tubal ligation as a single method):
• Use of a double-barrier method of contraception: condoms (male or female) and a diaphragm or cervical cap with spermicide;
• Use of an intrauterine device (IUD) and a barrier method: condoms (male or female, with or without spermicide) or a diaphragm or cervical cap with spermicide;
• For those in the imatinib only study arms: use of hormone-based contraceptives (pill, patch, implant, ring, or injectable) and a barrier method: condoms (male or female, with or without spermicide) or a diaphragm or cervical cap with spermicide (participants in study arms receiving isoniazid and rifabutin are not eligible if they are relying hormonal contraceptives other than an IUD)
• Tubal ligation.
• Women who are post-menopausal, defined as age greater than 45 and no menses for at least 1 year, or who have had a hysterectomy, are considered not of reproductive potential.

Exclusion Criteria

• Current or imminent treatment for significant infection
• Pregnant or breastfeeding
• HIV positive status as determined by a U.S. Food and Drug Administration (FDA)-approved HIV assay
• Hepatitis B infection, as determined by an FDA-approved hepatitis B surface antigen assay
• Hepatitis C infection, as determined by an FDA-approved positive Hepatitis C antibody assay
• Known infection with Mycobacterium tuberculosis (MTB)
• History of allergy or hypersensitivity to imatinib, isoniazid or rifabutin.
• History of enrollment in other clinical trials with investigational agents within 8 weeks
• Cardiac arrhythmia requiring medication, or any clinically significant electrocardiogram (ECG) abnormality
• Exam consistent with congestive heart failure (e.g., edema)
• Random blood glucose greater than 140 mg/dL or history of unstable diabetes mellitus requiring hospitalization for hyper or hypoglycemia within the past year prior to start of screening
• Use of systemic corticosteroids within the past 28 days
• Any of the following readings from a complete blood count that fall outside the normal ranges as listed here:
• White blood cell count: 3.4 10E3/microliter (mcL) - 11 10E3/mcL
• Hemoglobin: Female- 11.1 - 16.7 gm/dL, Male- 12.5 - 16.5 gm/dL
• Platelet count: 150-400 10E3/mcL
• Absolute neutrophil count: Female- 0.91-5.53 10E3/mcL, Male- 0.67-6.41 10E3/mcL
• Absolute lymphocyte count: Female- 0.65-3.05 10E3/mcL, Male- 0.72-3.29 10E3/mcL
• Any of the following chemistry panel and liver function test readings that fall outside the normal ranges as listed here:
• Serum potassium: 3.5-5.4 mmol/L
• Alkaline phosphatase (ALP): 34 - 104 unit/L
• Alanine aminotransferase (ALT): 4 - 52 unit/L
• Aspartate aminotransferase (AST): 13 - 39 unit/L
• Total Bilirubin: 0.2 - 1.0 mg/dL
• Creatinine: Female- 0.60-1.20 mg/dL, Male- 0.7-1.3mg/dL
• Cirrhosis of the liver, or any known active or chronic liver disease
• Current or past alcohol or elicit/recreational drug use, which in the expert judgment of the Investigator, will interfere with the participant's ability to comply with the protocol requirements.
• Any experimental medications for less than 8 weeks prior to screening or anticipated use during the trial
• Current (within 30 days prior to the first dose of study drug) or anticipated use of antimetabolites; alkylating agents; or other drugs or herbal preparations (including St. John's wort), known to affect activity of the CYP3A4 enzyme pathway