Chronic Myelogenous LeukemiaPhase 1NCT01130688
Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in CML.
A Phase 1 study testing Zileuton in people with Chronic Myelogenous Leukemia, run by University of Massachusetts, Worcester at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous Leukemia
- What is being tested?
- Zileuton
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Dec 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic Myelogenous Leukemia
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. Shaoguang 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.
Read the 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. 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.
- Conditions
- Chronic Myelogenous Leukemia
- Being tested
- Zileuton
- Keywords
- Leukemia, Zileuton, myeloproliferative neoplasm
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZileutonDrug
Also called Zyflo
Imatinib combined with Zileuton
| Study group | Role | What they receive |
|---|---|---|
| single arm of experimental drug combination | Experimental | Not described Receives: Drug: Zileuton |
What is being measured
The primary outcome is the main question the study is designed to answer.
To define toxicity and safety profile of zileuton combined with imatinib in patients with CML
Measured: Throughout the study
Secondary outcomes (1)
To assess the efficacy of zileuton combined with imatinib in terms of (See Description)
- Level of 5-lipoxygenase (5-LO) blockade
- The rate of complete hematological response
- The rate of complete cytogenetic response
- The rate of major molecular response
Measured: Throughout the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study startJan 2010
- Primary completionOct 2012
- Study completionDec 2014
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jan Cerny, University of Massachusetts, Worcester
- Investigators
- Jan Cerny, MD, PhD, Principal investigator, University of Massachusetts, Worcester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01130688
- Sponsor's protocol ID
- UM200905
- Status last verified
- Jan 2013
- First submitted
- 24 May 2010
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1038/ng.389. Epub 2009 Jun 7.
PubMed 19503090Druker 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. doi: 10.1056/NEJMoa062867.
PubMed 17151364
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT01130688
- Acronym / sponsor ID
- UM200905
- Conditions
- Chronic Myelogenous Leukemia
- Keywords
- Leukemia, Zileuton, myeloproliferative neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 26 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Shaoguang 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.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm of experimental drug combination | Experimental | Drug: Zileuton |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZileutonAlso: ZyfloImatinib combined with Zileuton | Drug | single arm of experimental drug combination |
Primary outcome
To define toxicity and safety profile of zileuton combined with imatinib in patients with CML
Time frame: Throughout the study
1 secondary outcome
To assess the efficacy of zileuton combined with imatinib in terms of (See Description)
Time frame: Throughout the study
Results and safety
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
- Results publication: PubMed 19503090Chen 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.
- Results publication: PubMed 17151364Druker 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. doi: 10.1056/NEJMoa062867.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Cerny, MD, PhD principal investigator
University of Massachusetts, Worcester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zileuton in people with Chronic Myelogenous Leukemia, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To define toxicity and safety profile of zileuton combined with imatinib in patients with CML (time frame: Throughout the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01130688, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2015.