NCT02883036

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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 19, 2016

Completed
11 days until next milestone

First Posted

Study publicly available on registry

August 30, 2016

Completed
2 days until next milestone

Study Start

First participant enrolled

September 1, 2016

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2021

Completed
Last Updated

August 30, 2016

Status Verified

August 1, 2016

Enrollment Period

5 years

First QC Date

August 19, 2016

Last Update Submit

August 24, 2016

Conditions

Keywords

tigecyclinetreatmentmitochondrial biogenesismetabolic characteristics

Outcome Measures

Primary Outcomes (1)

  • mitochondrial biogenesis and metabolic characteristics of Bone Marrow(BM)/ Peripheral Blood(PB) mononuclear cells

    Through study completion, an average of 1 year

Secondary Outcomes (3)

  • mitochondrial biogenesis and metabolic characteristics of BM/PB mononuclear cells after tigecycline stimulation

    After Hour 24 and 48 tigecycline stimulation

  • cell viability and apoptosis of BM/PB mononuclear cells after tigecycline stimulation

    After Hour 24 and 48 tigecycline stimulation

  • Patients' clinical characteristics and survival outcomes

    Through study completion, an average of 1 year

Study Arms (2)

Patients with chronic myeloid leukemia

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

Other: blood sampling

Healthy volunteers

Healthy volunteers

Other: blood sampling

Interventions

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

Patients with chronic myeloid leukemia

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

100 adults patients with chronic myeloid leukemia

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of hematology,Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

Related 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. doi: 10.18632/oncotarget.3174.

    PMID: 25625193BACKGROUND
  • 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.

    PMID: 22094260BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

mononuclear cells of bone marrow and/or peripheral blood

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Central Study Contacts

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
professor

Study Record Dates

First Submitted

August 19, 2016

First Posted

August 30, 2016

Study Start

September 1, 2016

Primary Completion

September 1, 2021

Last Updated

August 30, 2016

Record last verified: 2016-08

Locations