Vitro Study of Tigecycline to Treat Chronic Myeloid Leukemia

Chronic Myeloid Leukemia Clinical Trial

Official title:

Changes of Mitochondrial Biogenesis and Metabolic Characteristics About Tigecycline to Treat Chronic Myeloid Leukemia in Vitro

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02883036
• Other study ID #: VSTICML-01
• Status: Not yet recruiting
• Phase: N/A
• First received: August 19, 2016
• Last updated: August 24, 2016
• Start date: September 2016

Study information

• Verified date: August 2016
• Source: Nanfang Hospital of Southern Medical University
• Contact: Xiaoli Liu, MD
• Phone: 86-020-61641616
• Email: lxl2405[@]126.com
• Is FDA regulated: No
• Health authority: China:medical ethics committee of Nanfang Hospital
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Other:
• blood sampling
sampling after diagnosis and the mononuclear cells will be given tigecycline stimulation in vitro
• blood sampling
sampling after register and the mononuclear cells will be given tigecycline stimulation in vitro

Locations

Country	Name	City	State
China	Department of hematology,Nanfang Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mitochondrial biogenesis and metabolic characteristics of Bone Marrow(BM)/ Peripheral Blood(PB) mononuclear cells		Through study completion, an average of 1 year	No
Secondary	mitochondrial biogenesis and metabolic characteristics of BM/PB mononuclear cells after tigecycline stimulation		After Hour 24 and 48 tigecycline stimulation	No
Secondary	cell viability and apoptosis of BM/PB mononuclear cells after tigecycline stimulation		After Hour 24 and 48 tigecycline stimulation	No
Secondary	Patients' clinical characteristics and survival outcomes		Through study completion, an average of 1 year	No