Vitro Study of Tigecycline to Treat Chronic Myeloid Leukemia

NCT ID: NCT02883036

Last Updated: 2016-08-30

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-09-30

Brief Summary

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm companies with the BCR-ABL fusion gene encoded by the Philadelphia (Ph) chromosome. The BCR-ABL fusion protein(the formation of the chimeric gene BCR/ABL on chromosome 22 and a reciprocal ABL/BCR on chromosome 9,it has no expanded name) plays key role on CML leukemogenesis by activating its downstream signaling pathway of survival and proliferation. Imatinib, a targeted competitive inhibitor of a BCR-ABL tyrosine kinase, changed the clinical treatment and prognosis of CML. As its optimized generation, other tyrosine kinase inhibitors (TKIs), dasatinib and nilotinib have more potent anti-leukemic activity and less side-effect. However, acquired resistance to TKIs is one of the main obstacles to effective CML treatment and is involved in gene amplication of ABL tyrosine kinase point mutations. The outcomes of patients with these ABL tyrosine kinase point mutations have linked to worse prognosis and higher mortality generally. Metabolic adaptations are common in cancer cells, and cancer cells become more dependent on mitochondrial biogenesis. Tigecycline, as a broad-spectrum antibiotics, inhibits mitochondrial biogenesis as its an interesting "side-effect".In recent study,researchers indicated that tigecycline can eradicate cancer stem cells by targeting mitochondrial.Here, the investigators test tigecycline's anti-leukemic activity to chronic myeloid leukemia in vitro.

Detailed Description

In this study, the investigators collected bone marrow(BM) or/and peripheral blood(PB) mononuclear cells from patients with chronic myeloid leukemia.Patients could be in different stages of chronic myeloid leukemia pre-treatment.Additionally, the investigators also selected some healthy volunteers as comparison.Firstly, the investigators analyzed mitochondrial biogenesis and basal metabolic characteristic of mononuclear cells from patients and healthy volunteers.Secondly, the investigators tested the cell viability and apoptosis after tigecycline treatment.Thirdly,the investigators detected the changes of cell mitochondrial biogenesis and metabolic characteristic in the same study sample after tigecycline stimulation. Finally,the investigators analyzed the correlation between sensitivities of mononuclear cells to tigecycline and patients' clinical parameters and survival outcome.

Conditions

Chronic Myeloid Leukemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with chronic myeloid leukemia

100 adult patients(age\>18 years),with chronic myeloid leukemia defined by the World Health Organization(WHO) criteria

blood sampling

Intervention Type: OTHER

sampling after diagnosis and the mononuclear cells will be given tigecycline stimulation in vitro

Healthy volunteers

Healthy volunteers

blood sampling

Intervention Type: OTHER

sampling after register and the mononuclear cells will be given tigecycline stimulation in vitro

Interventions

blood sampling

sampling after diagnosis and the mononuclear cells will be given tigecycline stimulation in vitro

Intervention Type: OTHER

blood sampling

sampling after register and the mononuclear cells will be given tigecycline stimulation in vitro

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive CML confirmed by cytogenetic and/or molecular analysis;
• Age >18 years.
• Eligibility of patients receiving any medications or substances known to affect or determined following review of their case by the Principal Investigator

Exclusion Criteria

• Patients may not receive any other antibiotics.
• Patients may not have received prior treatment with TKIs or hydroxyurea.
• Major cognitive deficits or psychiatric problems hampering a self-reported evaluation.
• No prior malignancies or any other cancer from which patient has been disease free for 5 years.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: lead

Responsible Party

Xiaoli Liu

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of hematology,Nanfang Hospital

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Xiaoli Liu, MD

Role: CONTACT

lxl2405@126.com

86-020-61641616

Na Xu, MD

Role: CONTACT

292347668@qq.com

86-020-61641615

Facility Contacts

Xiaoli Liu, MD

Role: primary

lxl2405@126.com

86-020-61641616

Na Xu, MD

Role: backup

292347668@qq.com

86-020-61641615

References

Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget. 2015 Mar 10;6(7):4569-84. doi: 10.18632/oncotarget.3174.

Reference Type: BACKGROUND

PMID: 25625193 (View on PubMed)

Skrtic M, Sriskanthadevan S, Jhas B, Gebbia M, Wang X, Wang Z, Hurren R, Jitkova Y, Gronda M, Maclean N, Lai CK, Eberhard Y, Bartoszko J, Spagnuolo P, Rutledge AC, Datti A, Ketela T, Moffat J, Robinson BH, Cameron JH, Wrana J, Eaves CJ, Minden MD, Wang JC, Dick JE, Humphries K, Nislow C, Giaever G, Schimmer AD. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell. 2011 Nov 15;20(5):674-88. doi: 10.1016/j.ccr.2011.10.015.

Reference Type: BACKGROUND

PMID: 22094260 (View on PubMed)

Other Identifiers

VSTICML-01

Identifier Type: -

Identifier Source: org_study_id