Use of SV40 Vectors to Treat Chronic Myeloid Leukemia (CML)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00257647
First received: November 22, 2005
Last updated: February 17, 2009
Last verified: April 2007

November 22, 2005
February 17, 2009
September 2005
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Complete list of historical versions of study NCT00257647 on ClinicalTrials.gov Archive Site
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Use of SV40 Vectors to Treat Chronic Myeloid Leukemia (CML)
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.

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.

Observational
Time Perspective: Prospective
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Non-Probability Sample

CML patients which were seen at Hadassah hospital.

Chronic Myeloid Leukemia
Other: SV40 vectors carrying siRNA
in vitro only use of gene therapy
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
November 2007
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Inclusion Criteria:

  • Diagnosis of CML

Exclusion Criteria:

  • Under 18 years old
  • Pregnant
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Israel
 
NCT00257647
497169-HMO-CTIL, US Army
No
Ariella Oppenheim, Hadassah Medical Organization
Hadassah Medical Organization
Department of Defense
Study Chair: Deborah G Rund, MD Hadassah Medical Organization
Principal Investigator: Ariella Oppenheim, PhD Hadassah Medical Organization
Hadassah Medical Organization
April 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP