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

NCT01130688 | Terminated Phase 1

• 1 other identifier: UM200905
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myelogenous Leukemia

Keywords

Leukemia; Zileuton; myeloproliferative neoplasm

Outcome Measures

Primary Outcomes (1)

• To define toxicity and safety profile of zileuton combined with imatinib in patients with CML

  Throughout the study

Secondary Outcomes (1)

• To assess the efficacy of zileuton combined with imatinib in terms of (See Description)

  Throughout the study

Study Arms (1)

single arm of experimental drug combination

EXPERIMENTAL

Drug: Zileuton

Interventions

Zileuton DRUG

Imatinib combined with Zileuton

Also known as: Zyflo

single arm of experimental drug combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Related Publications (2)

• Chen 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 RESULT

• Druker 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 RESULT

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Myeloproliferative Disorders

Interventions

zileuton

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Cerny, MD, PhD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2010
• First Posted: May 26, 2010
• Study Start: January 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2014
• Last Updated: May 27, 2015

Record last verified: 2013-01

Locations

US (1)