Clinical trial · Interventional
Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in CML.
Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic Myelogenous Leukemia
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Lack of enrollment
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Chronic Myelogenous Leukemia | Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Zileuton | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- single arm of experimental drug combination
- interventionNames
- Drug: Zileuton
Primary outcomes (1)
- measure
- To define toxicity and safety profile of zileuton combined with imatinib in patients with CML
- timeFrame
- Throughout the study
Secondary outcomes (1)
- measure
- To assess the efficacy of zileuton combined with imatinib in terms of (See Description)
- timeFrame
- Throughout the study
- description
- * Level of 5-lipoxygenase (5-LO) blockade * The rate of complete hematological response * The rate of complete cytogenetic response * The rate of major molecular response
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (2)
- RESULTChen Y, Hu Y, Zhang H, Peng C, Li S. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nat Genet. 2009 Jul;41(7):783-92. doi: 10.1038/ng.389. Epub 2009 Jun 7. PMID 19503090
- RESULTDruker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006 Dec 7;355(23):2408-17. doi: 10.1056/NEJMoa062867. PMID 17151364