NCT02047149

Evaluating the Safety of Zileuton (Zyflo®) in Combination With Dasatinib (Sprycel®) in Chronic Myelogenous Leukemia

Phase I Study to Evaluate the Safety of Zileuton (Zyflo®) in Combination With Dasatinib (Sprycel®) in Patients With Chronic Myelogenous Leukemia

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: University of Massachusetts, Worcester · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Prospective nonrandomized phase I study The purpose of this study is to determine safety and efficacy of zileuton when added to dasatinib in patients with chronic myelogenous leukemia (CML).

Detailed description

The standard treatment for chronic myelogenous leukemia is therapy with tyrosine kinase inhibitors (TKIs). This treatment can diminish the amount of disease to very low levels that only very sensitive and specialized techniques can measure; it does not, however, provide a cure. Dr. Shaoguang Li and colleagues at University of Massachusetts have published a unique discovery that the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) is a critical regulator for LSCs in BCR-ABL-induced CML (Chen Y et al. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nature Genetics 41:783-792, 2009). In the absence of Alox5, BCR-ABL failed to induce CML in preclinical studies. While deficiency in Alox5 had no effect on normal hematopoiesis, impairment of the LSCs function through differentiation and cell division of CML LSCs was observed. This defect led to a depletion of LSCs and a failure of CML development. Treatment with a 5-LO inhibitor (zileuton) also impaired the function of LSCs and prolonged survival. These results demonstrate that a specific target gene can be found in cancer stem cells and its inhibition can completely inhibit the function of these stem cells. These findings provide an exciting opportunity to develop the first anti-cancer stem cell therapy for treating CML. Patients who did not respond or did not tolerate two TKIs will be considered for this study.

Conditions

• Chronic Myelogenous Leukemia

Interventions

Type	Name	Description
DRUG	Zileuton (Zyflo®) Dasatinib (Sprycel®)	To determine the maximum dose of zileuton/dasatinib in subjects with CML
DRUG	Dosing with Zileuton/Dasatinib in CML	Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD
DRUG	Daily dosing of Zileuton/Dasatinib	Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD
DRUG	Daily dosing with Zileuton/Dasatinib for CML	Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Timeline

• Start date: 2014-01-01
• Primary completion: 2016-06-01
• Completion: 2016-06-01
• First posted: 2014-01-28
• Last updated: 2016-09-30

Locations

1 site across 1 country: United States