Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in CML.

• Status: Terminated
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The leukemic stem cells (LSCs) are cells that self- renew and give rise to leukemia. Eradication of LSC is required for cure. In chronic myelogenous leukemia (CML) LSCs are not eradicated by imatinib (Gleevec) alone. Recent discovery by Dr. Shaoguang Li at University of Massachusetts indicates that the LSCs can be targeted by a new drug zileuton (Chen et al. Nature Genetics 2009; 41:783-792). Zileuton (approved for asthma) will be tested in a combination with Gleevec. This combination has not been used previously to treat leukemia.

This is a Phase I study. The goal of this research is to evaluate the safety of the standard anti-cancer drug imatinib and experimental drug zileuton.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Massachusetts, Worcester
• Treatments: Hydroxyurea; Imatinib Mesylate; Zileuton

Criteria

Inclusion Criteria:

• Patients with CML in chronic phase (patients already on imatinib)

• Presence of Philadelphia chromosome or bcr-abl rearrangement

• Age ≥ 18 years

• ECOG performance status ≤ 2

• Written informed consent

Exclusion Criteria:

• Hepatic dysfunction (serum bilirubin ≥ 2 x ULN, and/or ALT ≥ 3 x ULN, and/or AST ≥ 3 x ULN)

• Renal dysfunction (creatinine ≥ 200 μmol/l or 2.3 mg/dl)

• Severe cardiac dysfunction (NYHA classification III-IV)

• Severe pulmonary or neurologic disease

• Pregnant or lactating females

• Patients with a history of active malignancy during the past 5 years with the exception of nonmetastatic skin cancer (e.g. treated squamous or basal cell carcinoma) or stage 0 cervical carcinoma

• Patients known to be HIV-positive

• Patients with active, uncontrolled infections

• Male and female patients of reproductive potential who are not practicing effective means of contraception

• Patients with known allergic reaction or intolerance to either imatinib or zileuton

• Patients requiring anticoagulation therapy with coumadin