NCT02047149

Brief 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).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2014

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

January 24, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 28, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

September 30, 2016

Status Verified

September 1, 2016

Enrollment Period

2.4 years

First QC Date

January 24, 2014

Last Update Submit

September 29, 2016

Conditions

Chronic Myelogenous Leukemia

Keywords

Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

  • To determine the maximal tolerated dose (MTD) of zileuton when added to dasatinib in patients with CML

    36 mos

Secondary Outcomes (1)

  • To assess the efficacy of zileuton combined with dasatinib in terms of:

    36 mos

Study Arms (1)

Zileuton/Dasatinib

EXPERIMENTAL

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

Drug: Zileuton (Zyflo®) Dasatinib (Sprycel®)Drug: Dosing with Zileuton/Dasatinib in CMLDrug: Daily dosing of Zileuton/DasatinibDrug: Daily dosing with Zileuton/Dasatinib for CML

Interventions

Zileuton (Zyflo®) Dasatinib (Sprycel®)DRUG

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

Zileuton/Dasatinib
Dosing with Zileuton/Dasatinib in CMLDRUG

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

Also known as: Zyflo® + Sprycel®
Zileuton/Dasatinib
Daily dosing of Zileuton/DasatinibDRUG

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

Also known as: Zyflo® + Sprycel®
Zileuton/Dasatinib
Daily dosing with Zileuton/Dasatinib for CMLDRUG

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

Also known as: Zyflo®, Sprycel®
Zileuton/Dasatinib

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Target Population:
  • \. 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

You may not qualify if:

  • 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
  • Target Population
  • Patients intolerant of dasatinib.
  • 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)
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Related Publications (3)

  • 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: 19503090BACKGROUND

  • Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12. doi: 10.1200/JCO.2007.14.9260. Epub 2008 Jun 9.

    PMID: 18541900BACKGROUND

  • Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990 Feb 16;247(4944):824-30. doi: 10.1126/science.2406902.

    PMID: 2406902BACKGROUND

Related Links

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, Myeloid

Interventions

zileutonDasatinib

Condition Hierarchy (Ancestors)

LeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidines

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
MD, PhD, Assistant Professor, Medicine

Study Record Dates

First Submitted

January 24, 2014

First Posted

January 28, 2014

Study Start

January 1, 2014

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

September 30, 2016

Record last verified: 2016-09

Locations

US(1)