Chronic Myeloid LeukemiaNCT00257647
Use of SV40 Vectors to Treat Chronic Myeloid Leukemia (CML)
An observational study of Chronic Myeloid Leukemia, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
Chronic myeloid leukemia is a serious disease which is characterized by progression from relatively quiescent stages of the disease to an aggressive phase. Although now there is highly successful medical therapy known as Gleevec (Imatinib), the treatment is not always successful and patients do develop resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- SV40 vectors carrying siRNA
- How many people
- 25 participants
- Where
- 1 siteIsrael
- Study dates
- Sep 2005to Nov 2007
- Phase
- Observational
- 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
Study population: CML patients which were seen at Hadassah hospital.
Who may be able to join
- Diagnosis of CML
Who cannot join
- Under 18 years old
- Pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of SV40 siRNA Vectors to Treat CML
Chronic myeloid leukemia is a serious disease which is characterized by progression from relatively quiescent stages of the disease to an aggressive phase. Although now there is highly successful medical therapy known as Gleevec (Imatinib), the treatment is not always successful and patients do develop resistance. Those patients have limited treatment options. We are developing a gene therapy model of treatment for this disease using pseudoviral particles to insert molecules of genetic material which would not allow the harmful genes causing the leukemia to function.
Read the detailed description
A novel methodology that facilitates specific silencing of genes has recently been developed. The method is based on the property of small molecules of nucleic acids (RNA) to specifically repress expression of targeted genes. These small interfering RNA (siRNA) molecules were recently demonstrated to repress, in tissue culture cells, one of the two types of the common fusion genes present in CML patients. Those studies showed that treatment with synthetic siRNA inhibited cell growth and increased the sensitivity to imatinib. These findings offer hope that a novel form of gene therapy based on this strategy may improve the treatment outcome of CML patients, particularly when used in combination with other approaches such as the tyrosine kinase inhibitor imatinib that was mentioned above.
Our group has developed an innovative vector that is most suitable to deliver siRNA molecules into human hematopoietic cells with sufficient efficacy. The vector is based on a monkey virus called simian virus 40 (SV40). The viral coat, or capsid, is produced biosynthetically. It was engineered to self-assemble in the test tube around the nucleic acids of choice, and to deliver this DNA or RNA into target cells. This vector is safer than other available viral vectors since all the viral genetic material is excluded from the final product. The vector does not elicit immune response, thus allowing repeated administration.We will start the project by testing the recently published siRNA molecules against one of the fusion genes, and several alternative siRNA molecules that we will design against the other fusion genes. The molecules will be tested for efficacy in tissue culture cell-lines, by measuring repression of the respective fusion gene, reduction in the level of the tyrosine kinase and inhibition of cell growth. The most effective siRNA molecules will be selected for further studies. The vectors will be tested on cell-lines for gene silencing and cell death as before. At the final stage we will test the best vectors for their efficacy in white blood cells obtained from CML patients.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- SV40 vectors carrying siRNA
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SV40 vectors carrying siRNAOther
in vitro only use of gene therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2005 (estimated)
- Study startSep 2005
- Study completionNov 2007
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 Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Investigators
- Deborah G Rund, MD, Study chair, Hadassah Medical OrganizationAriella Oppenheim, PhD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00257647
- Sponsor's protocol ID
- 497169-HMO-CTIL
- Other IDs
- US Army
- Status last verified
- Apr 2007
- First submitted
- 22 Nov 2005
- Last updated
- 18 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Rund D, Dagan M, Dalyot-Herman N, Kimchi-Sarfaty C, Schoenlein PV, Gottesman MM, Oppenheim A. Efficient transduction of human hematopoietic cells with the human multidrug resistance gene 1 via SV40 pseudovirions. Hum Gene Ther. 1998 Mar 20;9(5):649-57. doi: 10.1089/hum.1998.9.5-649.
PubMed 9551613Kimchi-Sarfaty C, Ben-Nun-Shaul O, Rund D, Oppenheim A, Gottesman MM. In vitro-packaged SV40 pseudovirions as highly efficient vectors for gene transfer. Hum Gene Ther. 2002 Jan 20;13(2):299-310. doi: 10.1089/10430340252769815.
PubMed 11812285
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of SV40 siRNA Vectors to Treat CML
- ClinicalTrials.gov ID
- NCT00257647
- Acronym / sponsor ID
- 497169-HMO-CTIL
- Conditions
- Chronic Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Sep 2005
- Study completion
- Nov 2007 (actual)
- First posted
- 23 Nov 2005 (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.
Chronic myeloid leukemia is a serious disease which is characterized by progression from relatively quiescent stages of the disease to an aggressive phase. Although now there is highly successful medical therapy known as Gleevec (Imatinib), the treatment is not always successful and patients do develop resistance. Those patients have limited treatment options. We are developing a gene therapy model of treatment for this disease using pseudoviral particles to insert molecules of genetic material which would not allow the harmful genes causing the leukemia to function.
Detailed description
A novel methodology that facilitates specific silencing of genes has recently been developed. The method is based on the property of small molecules of nucleic acids (RNA) to specifically repress expression of targeted genes. These small interfering RNA (siRNA) molecules were recently demonstrated to repress, in tissue culture cells, one of the two types of the common fusion genes present in CML patients. Those studies showed that treatment with synthetic siRNA inhibited cell growth and increased the sensitivity to imatinib. These findings offer hope that a novel form of gene therapy based on this strategy may improve the treatment outcome of CML patients, particularly when used in combination with other approaches such as the tyrosine kinase inhibitor imatinib that was mentioned above.
Our group has developed an innovative vector that is most suitable to deliver siRNA molecules into human hematopoietic cells with sufficient efficacy. The vector is based on a monkey virus called simian virus 40 (SV40). The viral coat, or capsid, is produced biosynthetically. It was engineered to self-assemble in the test tube around the nucleic acids of choice, and to deliver this DNA or RNA into target cells. This vector is safer than other available viral vectors since all the viral genetic material is excluded from the final product. The vector does not elicit immune response, thus allowing repeated administration.We will start the project by testing the recently published siRNA molecules against one of the fusion genes, and several alternative siRNA molecules that we will design against the other fusion genes. The molecules will be tested for efficacy in tissue culture cell-lines, by measuring repression of the respective fusion gene, reduction in the level of the tyrosine kinase and inhibition of cell growth. The most effective siRNA molecules will be selected for further studies. The vectors will be tested on cell-lines for gene silencing and cell death as before. At the final stage we will test the best vectors for their efficacy in white blood cells obtained from CML patients.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- CML patients which were seen at Hadassah hospital.
Key inclusion criteria (1 listed)
- Diagnosis of CML
Key exclusion criteria (2 listed)
- Under 18 years old
- Pregnant
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 |
|---|---|---|
| SV40 vectors carrying siRNAin vitro only use of gene therapy | Other | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2009.
- Background: PubMed 9551613Rund D, Dagan M, Dalyot-Herman N, Kimchi-Sarfaty C, Schoenlein PV, Gottesman MM, Oppenheim A. Efficient transduction of human hematopoietic cells with the human multidrug resistance gene 1 via SV40 pseudovirions. Hum Gene Ther. 1998 Mar 20;9(5):649-57. doi: 10.1089/hum.1998.9.5-649.
- Background: PubMed 11812285Kimchi-Sarfaty C, Ben-Nun-Shaul O, Rund D, Oppenheim A, Gottesman MM. In vitro-packaged SV40 pseudovirions as highly efficient vectors for gene transfer. Hum Gene Ther. 2002 Jan 20;13(2):299-310. doi: 10.1089/10430340252769815.
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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.
Deborah G Rund, MD study chair
Hadassah Medical Organization
Ariella Oppenheim, PhD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Myeloid Leukemia, run by Hadassah Medical Organization at 1 site in Israel.
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 1 inclusion and 2 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: finished, as of the sponsor's last update on 18 Feb 2009. 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 Israel. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00257647, 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 18 Feb 2009.