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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT01130688

Chronic Myelogenous Leukemia

TERMINATED PHASE1

Efficacy and Safety Study of Dasatinib in Patients With Chronic Myeloid Leukemia

NCT00895297

Chronic Myeloid Leukemia

TERMINATED PHASE2

Pembrolizumab and Dasatinib, Imatinib Mesylate, or Nilotinib in Treating Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease

NCT03516279

Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Minimal Residual Disease

ACTIVE_NOT_RECRUITING PHASE2

A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia

NCT02011945

Chronic Myeloid Leukemia

COMPLETED PHASE1

An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

NCT01498445

Leukemia

TERMINATED PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Myelogenous Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Zileuton/Dasatinib

zileuton/dasatinib: This is a traditional phase I design. Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Group Type EXPERIMENTAL

Zileuton (Zyflo®) Dasatinib (Sprycel®)

Intervention Type DRUG

To determine the maximum dose of zileuton/dasatinib in subjects with CML

Dosing with Zileuton/Dasatinib in CML

Intervention Type DRUG

Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Daily dosing of Zileuton/Dasatinib

Intervention Type DRUG

Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Daily dosing with Zileuton/Dasatinib for CML

Intervention Type DRUG

Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Zileuton (Zyflo®) Dasatinib (Sprycel®)

To determine the maximum dose of zileuton/dasatinib in subjects with CML

Intervention Type DRUG

Dosing with Zileuton/Dasatinib in CML

Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Intervention Type DRUG

Daily dosing of Zileuton/Dasatinib

Three dose levels of daily zileuton will be studied in conjunction with dasatinib to define the MTD

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Zyflo® + Sprycel® Zyflo® + Sprycel® Zyflo® Sprycel®

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Target Population:

1\. Patients with CML with known inadequate response (as appropriate for their CML status) to TKIs or known resistance will be considered for this study

* Patients who are resistant or not responding adequately to dasatinib as a first line therapy, but are not able or eligible to receive other effective second line treatment can be considered for participation in the study.
* Age \> 18 years
* ECOG performance status ≤ 2
* Total bilirubin \< 2.0 times the institutional Upper Limit of Normal (ULN)
* Hepatic enzymes (AST, ALT ) ≤ 1.5 times the institutional ULN
* Serum Na, K+, Mg2+, Phosphate and Ca2+\>= Lower Limit of Normal (LLN)
* Serum Creatinine \< 2.3 mg/dL
* PT, PTT all Grade 0-1 3) Ability to take oral medication 4) Concomitant Medications
* Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy 5) Age and Sex
* Women of childbearing potential and men of fathering potential must use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy

Exclusion Criteria

1. Sex and Reproductive Status

* Women of childbearing potential and men of fathering potential unable or unwilling to use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy
2. Target Population

* Patients intolerant of dasatinib.
3. Medical History and Concurrent Diseases

* History of active malignancy during the past 5 years with the exception of nonmetastatic treated skin cancer (e.g. basal or squamous cell carcinoma ) or stage 0 cervical carcinoma
* Patients known to be HIV-positive
* Patients with active, uncontrolled infections
* Concurrent medical condition which may increase the risk of toxicity, including:
* Pleural or pericardial effusion of any grade
* Cardiac Conditions:
* Uncontrolled angina, congestive heart failure or MI within (6 months)
* Diagnosed congenital long QT syndrome
* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
* Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
* Severe cardiac dysfunction (NYHA classification III-IV)
* Severe pulmonary disease
* History of significant bleeding disorder unrelated to cancer
4. Physical and Laboratory Test Findings

* 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)
* Subjects with hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration
5. Allergies and Adverse Drug Reactions

* Patients with known allergic reaction or intolerance to either dasatinib or zileuton
6. Prohibited Treatments and/or Therapies

* Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
* quinidine, procainamide, disopyramide
* amiodarone, sotalol, ibutilide, dofetilide
* erythromycin, clarithromycin
* chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
* cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
* Patients requiring anticoagulation with Coumadin

* Prisoners or subjects who are involuntarily incarcerated.
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No