Chronic Lymphocytic LeukemiaNCT03150849
C-X-C Chemokine Receptor 4 in Chronic Lymphocytic Leukemia
An observational study of Chronic Lymphocytic Leukemia, run by Assiut University.
Trial summary
Chronic lymphocytic leukemia is the most common type of chronic leukemia, accounting for approximately 40% of all leukemias and mainly affecting older individuals. As it has a highly variable clinical course, identification of molecular and biological prognostic markers has provided new insights into the risk… Read more about this study
- Who is it for?
- Ages 20 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- C-X-C Chemokine Receptor 4
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2017to 1 Dec 2019
- 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 20 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: From Hematology clinic with chronic lynphocytic leukemia
Who may be able to join
- All patients are newly diagnosed as chronic lymphocytic leukemia
Who cannot join
- Patients with associated malignancies.
- Chronic lymphocytic leukemia patients on chemotherapy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: C-X-C Chemokine Receptor 4 as Prognostic Marker in Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia is the most common type of chronic leukemia, accounting for approximately 40% of all leukemias and mainly affecting older individuals. As it has a highly variable clinical course, identification of molecular and biological prognostic markers has provided new insights into the risk stratification of patients with chronic lymphocytic leukemia.
Read the detailed description
Prognosis depends primarily on the stage of the disease at diagnosis. There is a correlation between disease stage and median survival. However, about 50% of patients in early stage will develop more advanced disease. Also there is marked variation in disease progression amongst patients with similar Stages .
Extreme clinical heterogeneity is one of the hallmark features of chronic lymphocytic leukemia despite the identification of genetic and phenotypic markers that correlate with prognosis, the biological basis of this clinical variability remains unclear .. In addition, the interactions of chronic lymphocytic leukemia cells with the microenvironment in secondary lymphoid tissues and the bone marrow are known to promote chronic lymphocytic leukemia cell survival and proliferation.
The median age at diagnosis is 72 years, in the last decades chronic lymphocytic leukemia is more often diagnosed also in younger individuals, with almost 15% Of patients Of 55 years old or younger. There is a gender predisposition, As men are more frequently affected by chronic lymphocytic leukemia than women (male: female ratio of 1.5-2:1).
C-X-C chemokine receptor type 4 (CXCR4) is a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. Overexpression of C-X-C chemokine receptor type 4 is a hallmark of many hematological malignancies including acute myeloid leukemia, chronic lymphocytic leukemia and non-Hodgkin's lymphoma, and generally correlates with a poor prognosis. A highly potent competitive antagonist of C-X-C chemokine receptor type 4 recently has been identified with suppression of cancer cells aggressiveness in a variety of cancers.
The protein-coupled receptor C-X-C chemokine receptor type 4 is activated by stromal cell-derived factor 1 and is involved in the control of migration and homing of cells notably for engraftment of normal and neoplastic hematopoietic cells in the bone marrow (BM).
Bruton's tyrosine kinase (BTK) is a key player in B-cell antigen receptor (BCR) signaling that regulates B-cell growth. In addition to B-cell antigen receptor signaling, Bruton's tyrosine kinase participates in signal transduction through growth-factor receptors, Toll-like receptors, integrins and G-protein-coupled receptors such as C-X-C chemokine receptor type 4 and C-X-C chemokine receptor type 5. Bruton's tyrosine kinase inhibition results in impaired C-X-C chemokine receptor type 4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. inhibition of Bruton's tyrosine kinase function would lead to a loss of tumor volume by preventing replenishment after spontaneous or drug-induced death, and by subverting leukemia cell retention in and homing back to sustaining tissue niches. Decrease C-X-C chemokine receptor type 4 delays disease progression and prolongs survival
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- C-X-C Chemokine Receptor 4
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C-X-C Chemokine Receptor 4Diagnostic test
marker assessed by flowcytometry in a blood sample
| Study group | Role | What they receive |
|---|---|---|
| patient group | patient with chronic lymphocytic leukemia Receives: Diagnostic Test: C-X-C Chemokine Receptor 4 | |
| control group | healthy control group Receives: Diagnostic Test: C-X-C Chemokine Receptor 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The level of C-X-C Chemokine Receptor 4 in chronic lymphocytic leukemia patient and healthy individual
the level of C-X-C Chemokine Receptor 4 marker assessed by flowcytometry in a blood sample
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start1 Jul 2017 (estimated)
- Primary completion1 Jul 2019 (estimated)
- Study completion1 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed gamal, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150849
- Sponsor's protocol ID
- cxcll
- Status last verified
- May 2017
- First submitted
- 7 May 2017
- Last updated
- 12 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palmesino E, Moepps B, Gierschik P, Thelen M. Differences in CXCR4-mediated signaling in B cells. Immunobiology. 2006;211(5):377-89. doi: 10.1016/j.imbio.2005.12.003. Epub 2006 Apr 18.
PubMed 16716807Burger JA, Peled A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia. 2009 Jan;23(1):43-52. doi: 10.1038/leu.2008.299. Epub 2008 Nov 6.
PubMed 18987663Barretina J, Junca J, Llano A, Gutierrez A, Flores A, Blanco J, Clotet B, Este JA. CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease. Ann Hematol. 2003 Aug;82(8):500-505. doi: 10.1007/s00277-003-0679-0. Epub 2003 May 29.
PubMed 12783211Marchese A. Endocytic trafficking of chemokine receptors. Curr Opin Cell Biol. 2014 Apr;27:72-7. doi: 10.1016/j.ceb.2013.11.011. Epub 2013 Dec 14.
PubMed 24680433Domanska UM, Kruizinga RC, Nagengast WB, Timmer-Bosscha H, Huls G, de Vries EG, Walenkamp AM. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer. 2013 Jan;49(1):219-30. doi: 10.1016/j.ejca.2012.05.005. Epub 2012 Jun 9.
PubMed 22683307Vlad A, Deglesne PA, Letestu R, Saint-Georges S, Chevallier N, Baran-Marszak F, Varin-Blank N, Ajchenbaum-Cymbalista F, Ledoux D. Down-regulation of CXCR4 and CD62L in chronic lymphocytic leukemia cells is triggered by B-cell receptor ligation and associated with progressive disease. Cancer Res. 2009 Aug 15;69(16):6387-95. doi: 10.1158/0008-5472.CAN-08-4750. Epub 2009 Aug 4.
PubMed 19654311Li SH, Dong WC, Fan L, Wang GS. Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811. Am J Transl Res. 2016 Sep 15;8(9):3812-3821. eCollection 2016.
PubMed 27725861
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- C-X-C Chemokine Receptor 4 as Prognostic Marker in Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT03150849
- Acronym / sponsor ID
- cxcll
- Conditions
- Chronic Lymphocytic Leukemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jul 2017 (estimated)
- Primary completion
- 1 Jul 2019 (estimated)
- Study completion
- 1 Dec 2019 (estimated)
- First posted
- 12 May 2017 (actual)
- 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 lymphocytic leukemia is the most common type of chronic leukemia, accounting for approximately 40% of all leukemias and mainly affecting older individuals. As it has a highly variable clinical course, identification of molecular and biological prognostic markers has provided new insights into the risk stratification of patients with chronic lymphocytic leukemia.
Detailed description
Prognosis depends primarily on the stage of the disease at diagnosis. There is a correlation between disease stage and median survival. However, about 50% of patients in early stage will develop more advanced disease. Also there is marked variation in disease progression amongst patients with similar Stages .
Extreme clinical heterogeneity is one of the hallmark features of chronic lymphocytic leukemia despite the identification of genetic and phenotypic markers that correlate with prognosis, the biological basis of this clinical variability remains unclear .. In addition, the interactions of chronic lymphocytic leukemia cells with the microenvironment in secondary lymphoid tissues and the bone marrow are known to promote chronic lymphocytic leukemia cell survival and proliferation.
The median age at diagnosis is 72 years, in the last decades chronic lymphocytic leukemia is more often diagnosed also in younger individuals, with almost 15% Of patients Of 55 years old or younger. There is a gender predisposition, As men are more frequently affected by chronic lymphocytic leukemia than women (male: female ratio of 1.5-2:1).
C-X-C chemokine receptor type 4 (CXCR4) is a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. Overexpression of C-X-C chemokine receptor type 4 is a hallmark of many hematological malignancies including acute myeloid leukemia, chronic lymphocytic leukemia and non-Hodgkin's lymphoma, and generally correlates with a poor prognosis. A highly potent competitive antagonist of C-X-C chemokine receptor type 4 recently has been identified with suppression of cancer cells aggressiveness in a variety of cancers.
The protein-coupled receptor C-X-C chemokine receptor type 4 is activated by stromal cell-derived factor 1 and is involved in the control of migration and homing of cells notably for engraftment of normal and neoplastic hematopoietic cells in the bone marrow (BM).
Bruton's tyrosine kinase (BTK) is a key player in B-cell antigen receptor (BCR) signaling that regulates B-cell growth. In addition to B-cell antigen receptor signaling, Bruton's tyrosine kinase participates in signal transduction through growth-factor receptors, Toll-like receptors, integrins and G-protein-coupled receptors such as C-X-C chemokine receptor type 4 and C-X-C chemokine receptor type 5. Bruton's tyrosine kinase inhibition results in impaired C-X-C chemokine receptor type 4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. inhibition of Bruton's tyrosine kinase function would lead to a loss of tumor volume by preventing replenishment after spontaneous or drug-induced death, and by subverting leukemia cell retention in and homing back to sustaining tissue niches. Decrease C-X-C chemokine receptor type 4 delays disease progression and prolongs survival
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patient group | – | Diagnostic Test: C-X-C Chemokine Receptor 4patient with chronic lymphocytic leukemia |
| control group | – | Diagnostic Test: C-X-C Chemokine Receptor 4healthy control group |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- From Hematology clinic with chronic lynphocytic leukemia
Key inclusion criteria (1 listed)
- All patients are newly diagnosed as chronic lymphocytic leukemia
Key exclusion criteria (2 listed)
- Patients with associated malignancies.
- Chronic lymphocytic leukemia patients on chemotherapy
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 |
|---|---|---|
| C-X-C Chemokine Receptor 4marker assessed by flowcytometry in a blood sample | Diagnostic test | control group, patient group |
Primary outcome
The level of C-X-C Chemokine Receptor 4 in chronic lymphocytic leukemia patient and healthy individual
Time frame: 2 years
the level of C-X-C Chemokine Receptor 4 marker assessed by flowcytometry in a blood sample
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2017.
- Background: PubMed 16716807Palmesino E, Moepps B, Gierschik P, Thelen M. Differences in CXCR4-mediated signaling in B cells. Immunobiology. 2006;211(5):377-89. doi: 10.1016/j.imbio.2005.12.003. Epub 2006 Apr 18.
- Background: PubMed 18987663Burger JA, Peled A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia. 2009 Jan;23(1):43-52. doi: 10.1038/leu.2008.299. Epub 2008 Nov 6.
- Background: PubMed 12783211Barretina J, Junca J, Llano A, Gutierrez A, Flores A, Blanco J, Clotet B, Este JA. CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease. Ann Hematol. 2003 Aug;82(8):500-505. doi: 10.1007/s00277-003-0679-0. Epub 2003 May 29.
- Background: PubMed 24680433Marchese A. Endocytic trafficking of chemokine receptors. Curr Opin Cell Biol. 2014 Apr;27:72-7. doi: 10.1016/j.ceb.2013.11.011. Epub 2013 Dec 14.
- Background: PubMed 22683307Domanska UM, Kruizinga RC, Nagengast WB, Timmer-Bosscha H, Huls G, de Vries EG, Walenkamp AM. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer. 2013 Jan;49(1):219-30. doi: 10.1016/j.ejca.2012.05.005. Epub 2012 Jun 9.
- Background: PubMed 19654311Vlad A, Deglesne PA, Letestu R, Saint-Georges S, Chevallier N, Baran-Marszak F, Varin-Blank N, Ajchenbaum-Cymbalista F, Ledoux D. Down-regulation of CXCR4 and CD62L in chronic lymphocytic leukemia cells is triggered by B-cell receptor ligation and associated with progressive disease. Cancer Res. 2009 Aug 15;69(16):6387-95. doi: 10.1158/0008-5472.CAN-08-4750. Epub 2009 Aug 4.
- Background: PubMed 27725861Li SH, Dong WC, Fan L, Wang GS. Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811. Am J Transl Res. 2016 Sep 15;8(9):3812-3821. eCollection 2016.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Lymphocytic Leukemia, run by Assiut University.
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: status not confirmed, as of the sponsor's last update on 12 May 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eman mohamed salah, MD (01028030966, Emansalah.eldin@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The level of C-X-C Chemokine Receptor 4 in chronic lymphocytic leukemia patient and healthy individual (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03150849, which also lists 7 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 12 May 2017.