Chronic Myeloid LeukemiaNCT04818619
TIGIT in Patients With Chronic Myeloid Leukemia
An observational study of Chronic Myeloid Leukemia, run by Assiut University.
Trial summary
To expresse TIGIT in NK Cells in Patients with Chronic Myeloid Leukemia Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- flow cytometry test
- How many people
- 65 participants
- Where
- No sites listed yet
- Study dates
- Apr 2021to Dec 2022
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: the participants will be divided into 2 groups , 40 CML patients and 25 healthy individuals .
Who may be able to join
- CML patients
- Healthy individuals
Who cannot join
- Patients who have current or recent acute infection
- Patients who have autoimmune disease
- Patients who have diabetes mellitus disease
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Expression of TIGIT in NK Cells in Patients With Chronic Myeloid Leukemia
To expresse TIGIT in NK Cells in Patients with Chronic Myeloid Leukemia
Read the detailed description
Chronic myeloid leukemia (CML) is also known as chronic myelogenous leukemia. It's a type of cancer that starts in certain blood-forming cells of the bone marrow.
In CML, a genetic change takes place in an early (immature) version of myeloid cells that make red blood cells, platelets, and most types of white blood cells (except lymphocytes). This change forms an abnormal gene called BCR-ABL, which turns the cell into a CML cell. The leukemia cells grow and divide, building up in the bone marrow and spilling over into the blood. In time, the cells can also settle in other parts of the body, including the spleen. CML is a fairly slow growing leukemia, but it can change into a fast-growing acute leukemia that's hard to treat.
CML occurs mostly in adults, but very rarely it occurs in children, too. In general, their treatment is the same as for adults.
Chronic myeloid leukemia (CML) is characterized by the expression of the BCR/ABL1 fusion gene and the presence of the Philadelphia chromosome (Ph). The product of this fusion gene is a protein with deregulated tyrosine kinase activity, resulting in a malignant clonal disorder of the hematopoietic stem cells in the bone marrow (BM) and the accumulation of immature myeloid cells in peripheral blood (PB).
The use of tyrosine kinase inhibitors (TKIs) leads to a complete remission rate reaching 83%; however, mutation in the ABL kinase domain results in certain treatment failure. Furthermore, long-lasting side effects of treatment and the cost of TKIs remain a problem Therefore, the development of new TKI agents and combination therapies is urgently needed for CML patients .
Natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy.
The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells.
There is an abundance of evidence that NK cells can exhibit potent antitumor activity against CML, However, disease-associated mechanisms often inhibit the proper functions of endogenous NK cells, leading to inadequate tumor control and risk for disease progression.
As it is well known, the function of NK cells is precisely regulated by inhibitory and activating receptors.
Recently, T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine -based inhibitory motif (ITIM domain) (TIGIT) has been identified as a novel NK inhibitory receptor that can lead to NK cell exhaustion and dysfunction.
Targeting TIGIT is believed to restore 4 key function :Restoration of NK function, Depletion of T reg, Increase antigen-specific CD8 memory response and Induction of new antigen-specific CD8 T cells.
TIGIT was first identified as an inhibitory receptor expressed by activated CD4 Tcells , tregs and NK cells. However , direct evidence supporting a clinical role for TIGIT in AML.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- flow cytometry test
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flow cytometry testDiagnostic test
Blood samples will be stained with TIGIT by flow cytometry test
| Study group | Role | What they receive |
|---|---|---|
| chronic myeloid leukemia patients | Not described Receives: Diagnostic Test: flow cytometry test | |
| Healthy individuals | Not described Receives: Diagnostic Test: flow cytometry test |
What is being measured
The primary outcome is the main question the study is designed to answer.
TIGIT expression frequency on NK cells
In this study, we will assay the TIGIT expression frequency on NK cells in the peripheral blood of CML patients
Measured: 18 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study startApr 2021 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid 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
- Cross-sectional
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ola Abdelkarem Hasan, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04818619
- Sponsor's protocol ID
- chronic myeloid leukemia
- Status last verified
- Mar 2021
- First submitted
- 24 Mar 2021
- Last updated
- 29 Mar 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999 Jul 15;341(3):164-72. doi: 10.1056/NEJM199907153410306. No abstract available.
PubMed 10403855O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003 Mar 13;348(11):994-1004. doi: 10.1056/NEJMoa022457.
PubMed 12637609Heaney NB, Holyoake TL. Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol. 2007 Jun;25(2):66-75. doi: 10.1002/hon.813.
PubMed 17441215Lee HR, Baek KH. Role of natural killer cells for immunotherapy in chronic myeloid leukemia (Review). Oncol Rep. 2019 May;41(5):2625-2635. doi: 10.3892/or.2019.7059. Epub 2019 Mar 13.
PubMed 30896812Carlsten M, Jaras M. Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells. Front Immunol. 2019 Oct 11;10:2357. doi: 10.3389/fimmu.2019.02357. eCollection 2019.
PubMed 31681270Pizzolo G, Trentin L, Vinante F, Agostini C, Zambello R, Masciarelli M, Feruglio C, Dazzi F, Todeschini G, Chilosi M, et al. Natural killer cell function and lymphoid subpopulations in acute non-lymphoblastic leukaemia in complete remission. Br J Cancer. 1988 Sep;58(3):368-72. doi: 10.1038/bjc.1988.221.
PubMed 3179190Kiladjian JJ, Bourgeois E, Lobe I, Braun T, Visentin G, Bourhis JH, Fenaux P, Chouaib S, Caignard A. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia. 2006 Mar;20(3):463-70. doi: 10.1038/sj.leu.2404080.
PubMed 16408099Hughes A, Clarson J, Tang C, Vidovic L, White DL, Hughes TP, Yong AS. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017 Mar 2;129(9):1166-1176. doi: 10.1182/blood-2016-10-745992. Epub 2017 Jan 3.
PubMed 28049640
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expression of TIGIT in NK Cells in Patients With Chronic Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT04818619
- Acronym / sponsor ID
- chronic myeloid leukemia
- Conditions
- Chronic Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Apr 2021 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 26 Mar 2021 (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.
To expresse TIGIT in NK Cells in Patients with Chronic Myeloid Leukemia
Detailed description
Chronic myeloid leukemia (CML) is also known as chronic myelogenous leukemia. It's a type of cancer that starts in certain blood-forming cells of the bone marrow.
In CML, a genetic change takes place in an early (immature) version of myeloid cells that make red blood cells, platelets, and most types of white blood cells (except lymphocytes). This change forms an abnormal gene called BCR-ABL, which turns the cell into a CML cell. The leukemia cells grow and divide, building up in the bone marrow and spilling over into the blood. In time, the cells can also settle in other parts of the body, including the spleen. CML is a fairly slow growing leukemia, but it can change into a fast-growing acute leukemia that's hard to treat.
CML occurs mostly in adults, but very rarely it occurs in children, too. In general, their treatment is the same as for adults.
Chronic myeloid leukemia (CML) is characterized by the expression of the BCR/ABL1 fusion gene and the presence of the Philadelphia chromosome (Ph). The product of this fusion gene is a protein with deregulated tyrosine kinase activity, resulting in a malignant clonal disorder of the hematopoietic stem cells in the bone marrow (BM) and the accumulation of immature myeloid cells in peripheral blood (PB).
The use of tyrosine kinase inhibitors (TKIs) leads to a complete remission rate reaching 83%; however, mutation in the ABL kinase domain results in certain treatment failure. Furthermore, long-lasting side effects of treatment and the cost of TKIs remain a problem Therefore, the development of new TKI agents and combination therapies is urgently needed for CML patients .
Natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy.
The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells.
There is an abundance of evidence that NK cells can exhibit potent antitumor activity against CML, However, disease-associated mechanisms often inhibit the proper functions of endogenous NK cells, leading to inadequate tumor control and risk for disease progression.
As it is well known, the function of NK cells is precisely regulated by inhibitory and activating receptors.
Recently, T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine -based inhibitory motif (ITIM domain) (TIGIT) has been identified as a novel NK inhibitory receptor that can lead to NK cell exhaustion and dysfunction.
Targeting TIGIT is believed to restore 4 key function :Restoration of NK function, Depletion of T reg, Increase antigen-specific CD8 memory response and Induction of new antigen-specific CD8 T cells.
TIGIT was first identified as an inhibitory receptor expressed by activated CD4 Tcells , tregs and NK cells. However , direct evidence supporting a clinical role for TIGIT in AML.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| chronic myeloid leukemia patients | – | Diagnostic Test: flow cytometry test |
| Healthy individuals | – | Diagnostic Test: flow cytometry test |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- the participants will be divided into 2 groups , 40 CML patients and 25 healthy individuals .
Key inclusion criteria (2 listed)
- CML patients
- Healthy individuals
Key exclusion criteria (3 listed)
- Patients who have current or recent acute infection
- Patients who have autoimmune disease
- Patients who have diabetes mellitus disease
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 |
|---|---|---|
| flow cytometry testBlood samples will be stained with TIGIT by flow cytometry test | Diagnostic test | Healthy individuals, chronic myeloid leukemia patients |
Primary outcome
TIGIT expression frequency on NK cells
Time frame: 18 month
In this study, we will assay the TIGIT expression frequency on NK cells in the peripheral blood of CML patients
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Background: PubMed 10403855Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999 Jul 15;341(3):164-72. doi: 10.1056/NEJM199907153410306. No abstract available.
- Background: PubMed 12637609O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003 Mar 13;348(11):994-1004. doi: 10.1056/NEJMoa022457.
- Background: PubMed 17441215Heaney NB, Holyoake TL. Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol. 2007 Jun;25(2):66-75. doi: 10.1002/hon.813.
- Background: PubMed 30896812Lee HR, Baek KH. Role of natural killer cells for immunotherapy in chronic myeloid leukemia (Review). Oncol Rep. 2019 May;41(5):2625-2635. doi: 10.3892/or.2019.7059. Epub 2019 Mar 13.
- Background: PubMed 31681270Carlsten M, Jaras M. Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells. Front Immunol. 2019 Oct 11;10:2357. doi: 10.3389/fimmu.2019.02357. eCollection 2019.
- Background: PubMed 3179190Pizzolo G, Trentin L, Vinante F, Agostini C, Zambello R, Masciarelli M, Feruglio C, Dazzi F, Todeschini G, Chilosi M, et al. Natural killer cell function and lymphoid subpopulations in acute non-lymphoblastic leukaemia in complete remission. Br J Cancer. 1988 Sep;58(3):368-72. doi: 10.1038/bjc.1988.221.
- Background: PubMed 16408099Kiladjian JJ, Bourgeois E, Lobe I, Braun T, Visentin G, Bourhis JH, Fenaux P, Chouaib S, Caignard A. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia. 2006 Mar;20(3):463-70. doi: 10.1038/sj.leu.2404080.
- Background: PubMed 28049640Hughes A, Clarson J, Tang C, Vidovic L, White DL, Hughes TP, Yong AS. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017 Mar 2;129(9):1166-1176. doi: 10.1182/blood-2016-10-745992. Epub 2017 Jan 3.
Related trials for Chronic Myeloid Leukemia
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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 Myeloid 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 2 inclusion and 3 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 29 Mar 2021. 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 Ola Abdelkarem, M.B.B.Ch (00201066088250, olaabdelkarem1994@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TIGIT expression frequency on NK cells (time frame: 18 month). 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 NCT04818619, which also lists 8 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 29 Mar 2021.