Hi All,
Here is the criteria that was just posted on the NIH trial site for this Study....
Cheers,
Don
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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 ≥ 18 years
* ECOG performance status ≤ 2
* Written informed consent
Exclusion Criteria:
* 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)
* 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@umassmemorial.org
Contact: Alan Rosmarin, MD 508-334-7433 Alan.Rosmarin@umassmed.edu
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@umassmemorial.org
Contact: Alan Rosmarin, MD 508-334-7433 Alan.Rosmarin@umassmed.edu
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, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor 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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