Gleveec + Zileuton at UMass Trial Criteria

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Here is the criteria that was just posted on the NIH trial site for this

Study....

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

CML.

This study is currently recruiting participants.

Verified by University of Massachusetts, Worcester, June 2010

First Received: May 24, 2010 Last Updated: June 3, 2010 History of Changes

Sponsor: University of Massachusetts, Worcester

Information provided by: University of Massachusetts, Worcester

ClinicalTrials.gov Identifier: NCT01130688

Purpose

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. 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.

Condition Intervention Phase

Chronic Myelogenous Leukemia

Drug: Zileuton

Phase I

Study Type: Interventional

Study Design: Allocation: Non-Randomized

Control: Dose Comparison

Endpoint Classification: Safety/Efficacy Study

Intervention Model: Single Group Assignment

Masking: Open Label

Primary Purpose: Treatment

Official Title: Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in

Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic

Myelogenous Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Zileuton Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:

* To define toxicity and safety profile of zileuton combined with imatinib

in patients with CML [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

* To assess the efficacy of zileuton combined with imatinib in terms of (See

Description) [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

o Level of 5-lipoxygenase (5-LO) blockade

o The rate of complete hematological response

o The rate of complete cytogenetic response

o The rate of major molecular response

Estimated Enrollment: 15

Study Start Date: January 2010

Estimated Study Completion Date: December 2014

Estimated Primary Completion Date: December 2014 (Final data collection date

for primary outcome measure)

Intervention Details:

Drug: Zileuton

Imatinib combined with Zileuton

Detailed Description:

More than twenty two thousand people live with chronic myelogenous leukemia in

the United States and more than five thousand people are expected to be

diagnosed this year. The majority of patients with this disease are diagnosed in

what is called the chronic phase. The standard treatment for this phase of the

disease is therapy with a medication called imatinib. 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. 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.

Eligibility

Ages Eligible for Study: 18 Years and older

Genders Eligible for Study: Both

Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

* Patients with CML in chronic phase (patients already on imatinib)

* Presence of Philadelphia chromosome or bcr-abl rearrangement

* Age & #8805; 18 years

* ECOG performance status & #8804; 2

* Written informed consent

Exclusion Criteria:

* Hepatic dysfunction (serum bilirubin & #8805; 2 x ULN, and/or ALT & #8805; 3

x ULN, and/or AST & #8805; 3 x ULN)

* Renal dysfunction (creatinine & #8805; 200 & #956;mol/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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01130688

Contacts

Contact: Jan Cerny, MD, PhD 774-442-3903 Jan.Cerny@...

Contact: Alan Rosmarin, MD 508-334-7433 Alan.Rosmarin@...

Locations

United States, Massachusetts

University of Massachusetts Medical School Recruiting

Worcester, Massachusetts, United States, 01655

Contact: Jan Cerny, MD, PhD 774-442-3903 Jan.Cerny@...

Contact: Alan Rosmarin, MD 508-334-7433 Alan.Rosmarin@...

Principal Investigator: Jan Cerny, MD, PhD

Sponsors and Collaborators

University of Massachusetts, Worcester

Investigators

Principal Investigator: Jan Cerny, MD, PhD University of Massachusetts Medical

School

More Information

Publications:

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. Epub 2009 Jun 7.

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,

BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, T, Agis H,

Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP,

Simonsson B, 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.

Responsible Party: University of Massachusetts Medical School ( Jan Cerny, MD,

PhD )

ClinicalTrials.gov Identifier: NCT01130688 History of Changes

Other Study ID Numbers: UM200905

Study First Received: May 24, 2010

Last Updated: June 3, 2010

Health Authority: United States: Food and Drug Administration; United States:

Institutional Review Board

Keywords provided by University of Massachusetts, Worcester:

Leukemia

Zileuton

myeloproliferative neoplasm

Additional relevant MeSH terms:

Anti-Inflammatory Agents

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Hormone Antagonists

Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists

Protein Kinase Inhibitors

Leukotriene Antagonists

Leukemia

Sensory System Agents

Therapeutic Uses

Anti-Inflammatory Agents, Non-Steroidal

Analgesics

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Enzyme Inhibitors

Leukemia, Myeloid

Pharmacologic Actions

Lipoxygenase Inhibitors

Imatinib

Neoplasms

Analgesics, Non-Narcotic

Zileuton

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Peripheral Nervous System Agents

Bone Marrow Diseases

Antirheumatic Agents

Central Nervous System Agents

ClinicalTrials.gov processed this record on June 03, 2010

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