Chronic Myeloid Leukemia PatientsNCT03214718
Myeloid Derived Suppressor Cells and Chronic Myeloid Leukemia
A study testing Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day and Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day in people with Chronic Myeloid Leukemia Patients, run by Assiut University.
Trial summary
The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells , immature myeloid cells able to induce immune-escape, angiogenesis, and tumor… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Myeloid Leukemia Patients
- What is being tested?
- Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day and Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 5 Aug 2017to 5 Aug 2019
- Phase
- Interventional
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All newly diagnosed chronic phase CML patients during one year in Assiut university hospital.
Who cannot join
- Preivously diagnosed CML patients .
- Other myeloproliferative disorders .
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effect of Tyrosine Kinase Inhibitors on Myeloid Derived Suppressor Cells in Chronic Myeloid Leukemia Patients
The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells , immature myeloid cells able to induce immune-escape, angiogenesis, and tumor progression. Two different subpopulations have been identified and studied: granulocytic and monocytic myeloid derived suppressor cells with a different immunophenotype and immunosuppressive properties
Read the detailed description
Myeloid-derived suppressor cells utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of T cell activation and expansion . Human monocytic myeloid derived suppressor cells are mostly identified as CD14+ cells with negative or low expression of HLADR. And also express high levels of CD11b and CD33 antigen . Human granulocytic myeloid derived suppressor cells are usually defined as CD66b+ CD11b+ CD15+ HLADR- cells and display an intermediate expression of CD33 and a variable expression of CD11b, depending on their maturation stage .
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable deep molecular response as a prelude to successful treatment-free remission .
Accumulation of both Gr-MDSCs and Mo-MDSCs cells has been found in the peripheral blood of chronic myeloid leukemia (CML) patients. They are part of the tumor clone showing BCR/ABL expression.
BCR-ABL tyrosine kinase inhibitors (TKI) are able to induce remission in CML patients but not to eliminate leukemia stem cells , which can regenerate leukemia on drug discontinuation .
Unfortunately, molecular relapse is observed after cessation of tyrosine kinase inhibitors in 61-66% of CML patients, previously in complete molecular response (presumably due to the reactivation of dormant CML LSCs that are resistant to TKI-induced leukemic cell ablation. Thus, current research efforts aim to develop additional therapies to target these TKI-refractory CML LSCs .
With the aim of increasing cure rates and make it possible for patients to discontinue treatment, TKI therapies are currently evaluated in combination with immune modulators .
- Conditions
- Chronic Myeloid Leukemia Patients
- Being tested
- Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day, Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/dayDiagnostic test
For each patient these investigation will be done:
- Complete blood count,bone marrow aspirate and bone marrow biopsy Measure BCR-ABL GENE Level by FISH at diagnosis and every 3 months till one year .
Measurement Level of myeloid derived suppressor cells both granulocytic and monocytic cells by flowcytometry .
Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/dayDiagnostic test
For each patient these investigation will be done:
- Complete blood count,bone marrow aspirate and bone marrow biopsy Measure BCR-ABL GENE Level by FISH at diagnosis and every 3 months till one year .
Measurement Level of myeloid derived suppressor cells both granulocytic and monocytic cells by flowcytometry .
| Study group | Role | What they receive |
|---|---|---|
| CML patients treated with imatinib 400 mg/day | Experimental | Measurement of the level of myeloid derived suppressor cells (MDSCs) by flowctytometry for each newly diagnosed chronic phase chronic myeloid leukemia (CML) patients treated with imatinib 400 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene level and the sokal score of the patients and deep molecular response of the patients after one year . Receives: Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day |
| CML patients treated with nilotinib 600 mg/day | Active comparator | Measurement of the level of myeloid derived suppressor cells (MDSCs) for each newly diagnosed chronic phase chronic myeloid leukemia ( CML) patients treated with nilotinib 600 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene, the sokal score and deep molecular response of the patients after one year . Receives: Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of the different types of tyrosine kinase inhibitors (TKI) ( imatinib and nilotinib) therapy on MDSC and possible correlation with clinical response.
measuring response rate of patients on TKIs whether imatinib 400mg/ day or nilotinib 600 mg / day by assessment of level of BCR-ABL gene level measured by FISH in %every 3 months till one year. and correlate between this level and between level of MDSCs measured in % ,.Granulocytic MDSCs (G-MDSCs) were identified as CD11b+CD33+CD14-HLADR- cells, while the monocytic MDSCs (M-MDSCs) as CD14+HLADR by cytofluorimetric analysis also measured every 3 months till one year,and detect if there is decline in level of MDSCs after one year of TKIs therapy.
Measured: one years
Secondary outcomes (1)
Relation between the level of (MDSC) and clinical feature and sokal score of CML patients ..
correlate between MDSCs and clinical features of CML patients as spleen size measured in centimeters, haemoglobin level measured in gram/dl, sokal score of the patients exp (0.0116 x (age [years] - 43.4)) + (0.0345 x (spleen size [cm] - 7.51) + (0.188 x ((platelets [109/L]/700)^2 - 0.563)) + (0.0887 x (blasts [%] - 2.10)).
low-risk (Sokal score < 0.8), intermediate-risk (Sokal score 0.8 - 1.2) and high-risk (> 1.2 ) .
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start5 Aug 2017 (estimated)
- Primary completion5 Aug 2019 (estimated)
- Study completion5 Aug 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid Leukemia PatientsStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yomna Refaat Mahboub, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03214718
- Sponsor's protocol ID
- MDCSCML
- Status last verified
- Jul 2017
- First submitted
- 3 Jul 2017
- Last updated
- 11 Jul 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Brandau S, Moses K, Lang S. The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: cousins, siblings or twins? Semin Cancer Biol. 2013 Jun;23(3):171-82. doi: 10.1016/j.semcancer.2013.02.007. Epub 2013 Feb 28.
PubMed 23459190Giallongo C, Parrinello N, Tibullo D, La Cava P, Romano A, Chiarenza A, Barbagallo I, Palumbo GA, Stagno F, Vigneri P, Di Raimondo F. Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs) in chronic myeloid leukemia patients. PLoS One. 2014 Jul 11;9(7):e101848. doi: 10.1371/journal.pone.0101848. eCollection 2014.
PubMed 25014230Christiansson L, Soderlund S, Mangsbo S, Hjorth-Hansen H, Hoglund M, Markevarn B, Richter J, Stenke L, Mustjoki S, Loskog A, Olsson-Stromberg U. The tyrosine kinase inhibitors imatinib and dasatinib reduce myeloid suppressor cells and release effector lymphocyte responses. Mol Cancer Ther. 2015 May;14(5):1181-91. doi: 10.1158/1535-7163.MCT-14-0849. Epub 2015 Mar 11.
PubMed 25761894Xishan Z, Guangyu A, Yuguang S, Hongmei Z. The research on the immuno-modulatory defect of mesenchymal stem cell from Chronic Myeloid Leukemia patients. J Exp Clin Cancer Res. 2011 May 2;30(1):47. doi: 10.1186/1756-9966-30-47.
PubMed 21535879
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Tyrosine Kinase Inhibitors on Myeloid Derived Suppressor Cells in Chronic Myeloid Leukemia Patients
- ClinicalTrials.gov ID
- NCT03214718
- Acronym / sponsor ID
- MDCSCML
- Conditions
- Chronic Myeloid Leukemia Patients
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 5 Aug 2017 (estimated)
- Primary completion
- 5 Aug 2019 (estimated)
- Study completion
- 5 Aug 2019 (estimated)
- First posted
- 11 Jul 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.
The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells , immature myeloid cells able to induce immune-escape, angiogenesis, and tumor progression. Two different subpopulations have been identified and studied: granulocytic and monocytic myeloid derived suppressor cells with a different immunophenotype and immunosuppressive properties
Detailed description
Myeloid-derived suppressor cells utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of T cell activation and expansion . Human monocytic myeloid derived suppressor cells are mostly identified as CD14+ cells with negative or low expression of HLADR. And also express high levels of CD11b and CD33 antigen . Human granulocytic myeloid derived suppressor cells are usually defined as CD66b+ CD11b+ CD15+ HLADR- cells and display an intermediate expression of CD33 and a variable expression of CD11b, depending on their maturation stage .
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable deep molecular response as a prelude to successful treatment-free remission .
Accumulation of both Gr-MDSCs and Mo-MDSCs cells has been found in the peripheral blood of chronic myeloid leukemia (CML) patients. They are part of the tumor clone showing BCR/ABL expression.
BCR-ABL tyrosine kinase inhibitors (TKI) are able to induce remission in CML patients but not to eliminate leukemia stem cells , which can regenerate leukemia on drug discontinuation .
Unfortunately, molecular relapse is observed after cessation of tyrosine kinase inhibitors in 61-66% of CML patients, previously in complete molecular response (presumably due to the reactivation of dormant CML LSCs that are resistant to TKI-induced leukemic cell ablation. Thus, current research efforts aim to develop additional therapies to target these TKI-refractory CML LSCs .
With the aim of increasing cure rates and make it possible for patients to discontinue treatment, TKI therapies are currently evaluated in combination with immune modulators .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CML patients treated with imatinib 400 mg/day | Experimental | Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/dayMeasurement of the level of myeloid derived suppressor cells (MDSCs) by flowctytometry for each newly diagnosed chronic phase chronic myeloid leukemia (CML) patients treated with imatinib 400 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene level and the sokal score of the patients and deep molecular response of the patients after one year . |
| CML patients treated with nilotinib 600 mg/day | Active comparator | Diagnostic Test: Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/dayMeasurement of the level of myeloid derived suppressor cells (MDSCs) for each newly diagnosed chronic phase chronic myeloid leukemia ( CML) patients treated with nilotinib 600 mg/day before starting treatment and every 3 months till one year and correlate between it and level of BCR-ABL gene, the sokal score and deep molecular response of the patients after one year . |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- All newly diagnosed chronic phase CML patients during one year in Assiut university hospital.
Key exclusion criteria (2 listed)
- Preivously diagnosed CML patients .
- Other myeloproliferative disorders .
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 |
|---|---|---|
| Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/dayFor each patient these investigation will be done: - Complete blood count,bone marrow aspirate and bone marrow biopsy Measure BCR-ABL GENE Level by FISH at diagnosis and every 3 months till one year . Measurement Level of myeloid derived suppressor cells both granulocytic and monocytic cells by flowcytometry . | Diagnostic test | CML patients treated with imatinib 400 mg/day |
| Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/dayFor each patient these investigation will be done: - Complete blood count,bone marrow aspirate and bone marrow biopsy Measure BCR-ABL GENE Level by FISH at diagnosis and every 3 months till one year . Measurement Level of myeloid derived suppressor cells both granulocytic and monocytic cells by flowcytometry . | Diagnostic test | CML patients treated with nilotinib 600 mg/day |
Primary outcome
The effect of the different types of tyrosine kinase inhibitors (TKI) ( imatinib and nilotinib) therapy on MDSC and possible correlation with clinical response.
Time frame: one years
measuring response rate of patients on TKIs whether imatinib 400mg/ day or nilotinib 600 mg / day by assessment of level of BCR-ABL gene level measured by FISH in %every 3 months till one year. and correlate between this level and between level of MDSCs measured in % ,.Granulocytic MDSCs (G-MDSCs) were identified as CD11b+CD33+CD14-HLADR- cells, while the monocytic MDSCs (M-MDSCs) as CD14+HLADR by cytofluorimetric analysis also measured every 3 months till one year,and detect if there is decline in level of MDSCs after one year of TKIs therapy.
1 secondary outcome
Relation between the level of (MDSC) and clinical feature and sokal score of CML patients ..
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2017.
- Background: PubMed 23459190Brandau S, Moses K, Lang S. The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: cousins, siblings or twins? Semin Cancer Biol. 2013 Jun;23(3):171-82. doi: 10.1016/j.semcancer.2013.02.007. Epub 2013 Feb 28.
- Background: PubMed 25014230Giallongo C, Parrinello N, Tibullo D, La Cava P, Romano A, Chiarenza A, Barbagallo I, Palumbo GA, Stagno F, Vigneri P, Di Raimondo F. Myeloid derived suppressor cells (MDSCs) are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs) in chronic myeloid leukemia patients. PLoS One. 2014 Jul 11;9(7):e101848. doi: 10.1371/journal.pone.0101848. eCollection 2014.
- Background: PubMed 25761894Christiansson L, Soderlund S, Mangsbo S, Hjorth-Hansen H, Hoglund M, Markevarn B, Richter J, Stenke L, Mustjoki S, Loskog A, Olsson-Stromberg U. The tyrosine kinase inhibitors imatinib and dasatinib reduce myeloid suppressor cells and release effector lymphocyte responses. Mol Cancer Ther. 2015 May;14(5):1181-91. doi: 10.1158/1535-7163.MCT-14-0849. Epub 2015 Mar 11.
- Background: PubMed 21535879Xishan Z, Guangyu A, Yuguang S, Hongmei Z. The research on the immuno-modulatory defect of mesenchymal stem cell from Chronic Myeloid Leukemia patients. J Exp Clin Cancer Res. 2011 May 2;30(1):47. doi: 10.1186/1756-9966-30-47.
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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?
A study testing Measurement level of myeloid derived suppressor cells in CML patients treated with imatinibe 400 mg/day and Measurement level of myeloid derived suppressor cells in CML patients treated with nilotinib 600 mg/day in people with Chronic Myeloid Leukemia Patients, 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 11 Jul 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 yomna mahboub, MS (01006803088, yomna-rm@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The effect of the different types of tyrosine kinase inhibitors (TKI) ( imatinib and nilotinib) therapy on MDSC and possible correlation with clinical response. (time frame: one 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 NCT03214718, which also lists 4 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 11 Jul 2017.