Re: Gleveec + Zileuton at UMass Trial Criteria

[Guest guest]

Hi All,

Jerry Mayfield gave Dr Cerny permission to post trial updates on his site. Dr

Cerny told me he would be happy to post these same updates on any CML site, if

given permission. I'll leave that up to the moderator to let me know if you

want that to happen and I will get it done, otherwise, I can continue to provide

the updates.

Thanks my friends,

Don

Here is Dr Cerny's latest update to Jerry's site:

=====================================================================

Hello everyone!

First, let me thank you for your support, mentioning and discussing our research

and for following our research efforts. I see Mr. Adkins (Don) has already

shared with you some details about our CML study listed at:

http://clinicaltrials.gov/ct2/show/NCT01130688

I will be happy to answer questions that you may have regarding our current and

future studies. The information on the clinicaltrials website may be too

technical and I will do my best to explain everything.

1) I will be happy to participate in this discussion group and will check it

from time to time

2) I will also share some information on Twitter:

http://twitter.com/JanCernyMDPhD

3) I am working on a website which could also serve as another information

resource. I am hoping it would have a space for your comments. I will send you

the link once it is up.

4) I will be happy to answer more private questions via email or phone call.

Thank you once again.

Best,

Jan Cerny, MD, PhD

>

> Hi All,

>

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

Study....

>

> Don

>

>

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> Related Studies

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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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