Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06535113
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-29
Brief Title:
Decoding the Inflammasome Influence on Treatment Response in Acute Myeloid Leukemia
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Decoding the Inflammasome Influence on Treatment Response in Acute Myeloid Leukemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Inflamm-AML
Brief Summary:
The study is designed as a collection of biological samples of newly diagnosed acute myeloid leukemia AML patients treated in the clinical units involved Samples of peripheral blood PB and bone marrow BM will be analyzed to determine the Inflammasome profile before and after a first-line chemotherapy treatment
Detailed Description:
Acute myeloid leukemia AML is a highly aggressive and unfavorable malignancy primarily affecting bone marrow BM myeloid cells particularly in older individuals The standard treatment for fit intermediate and high-risk patients involves chemotherapy followed by allogeneic hematopoietic stem cell transplantation HSCT However around 60 of patients experience relapse requiring second-line therapies that offer a reduced likelihood of achieving a permanent cure
Inflammation significantly influences AML development progression leukemic cell behavior and treatment response Interactions between leukemic cells and microenvironment promote their growth survival and drug resistance The inflammasome an intracellular complex crucial for promoting inflammation triggers the release of the proinflammatory cytokines interleukin IL-1beta and IL-18 and induces pyroptosis inflammatory cell death in response to inflammatory stimuli There is growing evidence suggesting a link between the inflammasome and AML with components of the inflammasome being overexpressed in leukemic cells The precise mechanisms by which the inflammasome and its activation pathways influence AML still need to be fully understood
We speculate that excessive inflammasome activity in AML disrupts the balance of cytokine production leading to chronic inflammation which interferes with the normal development and function of hematopoietic cells in the BM microenvironment This heightened inflammasome signature could impact the way patients respond to chemotherapy potentially altering inflammatory processes ultimately reducing the efficacy of the treatment Variations in inflammasome activation among AML patients may explain differences in treatment outcomes including response rates hematopoietic recovery remission duration and overall survival
Understanding the molecular mechanisms involved in AML particularly the role of the inflammasome could allow a better disease risk stratification and the development of potential targeted therapies and interventions which could improve treatment outcomes More specifically identifying potential therapeutic targets within the inflammasome pathway may drive to the design of new treatment strategies precisely aimed at correcting inflammasome dysregulation in AML From the clinical point of view these insights could assist healthcare professionals in taking informed decisions in the management of AML patients By modulating inflammasome activity or targeting specific pathway components we could develop personalized treatment approaches tailored to individual patient needs optimizing treatment response and possibly minimizing chemotherapy-related side effects This personalized approach has the potential to enhance the quality of life for patients reduce complications and increase the overall effectiveness of treatments
During the Study period patients referring to the clinical centers will undergo the standard diagnostic and therapeutic process for their pathology according to international guidelines For all the patients that will agree to participate clinical data and biological samples will be analyzed for the aims of the Study The retrospective part of the data and material collection must have bio-banked material in compliance with the ethics and regulatory standards for the research purpose
Due to the Observational nature of the Study all diagnostic procedures and treatments applied are considered common practice All treatments comply with the ATC Code L01 the different schemes of treatment could be categorized under an intensive or non intensive protocol
Commonly used intensive induction regimens are
37 daunorubicine 60 mgm2 day 1-3 cytarabine as continue IV infusion 100200 mgm2 day 1-7
37 midostaurine 50 mg every 12 hours day 8-21
37 gemtuzumab ozogamicin 3 mgm2 day 1 4 7
CPX-351 daunorubicin 44 mgcytarabine 100 mg IV days 1 3 5 Commonly used intensive consolidation schemes include intermediatehigh dose cytarabine or CPX-351 Midostaurine gemtuzumab ozogamicin daunorubicine may be added as per guidelines
Non intensive induction and consolidation schemes include azaticidine 75 mgm2 day 1-7 Venetoclax at variable dose
For the retrospective collection of samples the preceding version of ELN guidelines 2017 will be appliedThe main hypothesis of the study is that an excessive inflammasome activity in AML disrupts the balance of cytokine production leading to a clinically relevant inflammatory state which interferes with the response to chemotherapy
In two years we plan to recruit 80 adult participants with a new diagnosis of AML undergoing first line chemotherapy treatment
The protocol is a multicenter national observational study indeed it is based on the Clinical Practice and is aimed at gathering information from the biological samples collected during the diagnosis process and after a first line treatment The Study will be prospective and retrospective The total duration of enrolment will be from August 2024 to January 2026 the observation period will be up to 6 months The information about the treatment and the assessment on disease responserelapseprogression will be collected for stratification and monitoring purpose Retrospectively specimens demographical and clinical information are retrieved from AML patients previously recruited by UO1 will be utilized Prospectively new AML patients will be recruited UO1 recruits AML patients collects biological samples at diagnosis and after chemotherapy processes and biobanks specimens and conducts functional inflammasome assays gene expression analysis and immunophenotyping of AML blasts in peripheral blood and bone marrow Additionally immunohistochemistry is performed on bone marrow biopsies UO2 recruits AML patients processes and cryobank specimens and ships samples to UO1 It also produce all diagnostic data for clinical standard of AML blasts in peripheral blood and bone marrow with immunohistochemistry conducted on bone marrow biopsies
The biological samples collected for the study include bone marrow biopsies and peripheral blood
Inflammation significantly influences AML development progression leukemic cell behavior and treatment response Interactions between leukemic cells and microenvironment promote their growth survival and drug resistance The inflammasome an intracellular complex crucial for promoting inflammation triggers the release of the proinflammatory cytokines interleukin IL-1beta and IL-18 and induces pyroptosis inflammatory cell death in response to inflammatory stimuli There is growing evidence suggesting a link between the inflammasome and AML with components of the inflammasome being overexpressed in leukemic cells The precise mechanisms by which the inflammasome and its activation pathways influence AML still need to be fully understood
We speculate that excessive inflammasome activity in AML disrupts the balance of cytokine production leading to chronic inflammation which interferes with the normal development and function of hematopoietic cells in the BM microenvironment This heightened inflammasome signature could impact the way patients respond to chemotherapy potentially altering inflammatory processes ultimately reducing the efficacy of the treatment Variations in inflammasome activation among AML patients may explain differences in treatment outcomes including response rates hematopoietic recovery remission duration and overall survival
Understanding the molecular mechanisms involved in AML particularly the role of the inflammasome could allow a better disease risk stratification and the development of potential targeted therapies and interventions which could improve treatment outcomes More specifically identifying potential therapeutic targets within the inflammasome pathway may drive to the design of new treatment strategies precisely aimed at correcting inflammasome dysregulation in AML From the clinical point of view these insights could assist healthcare professionals in taking informed decisions in the management of AML patients By modulating inflammasome activity or targeting specific pathway components we could develop personalized treatment approaches tailored to individual patient needs optimizing treatment response and possibly minimizing chemotherapy-related side effects This personalized approach has the potential to enhance the quality of life for patients reduce complications and increase the overall effectiveness of treatments
During the Study period patients referring to the clinical centers will undergo the standard diagnostic and therapeutic process for their pathology according to international guidelines For all the patients that will agree to participate clinical data and biological samples will be analyzed for the aims of the Study The retrospective part of the data and material collection must have bio-banked material in compliance with the ethics and regulatory standards for the research purpose
Due to the Observational nature of the Study all diagnostic procedures and treatments applied are considered common practice All treatments comply with the ATC Code L01 the different schemes of treatment could be categorized under an intensive or non intensive protocol
Commonly used intensive induction regimens are
37 daunorubicine 60 mgm2 day 1-3 cytarabine as continue IV infusion 100200 mgm2 day 1-7
37 midostaurine 50 mg every 12 hours day 8-21
37 gemtuzumab ozogamicin 3 mgm2 day 1 4 7
CPX-351 daunorubicin 44 mgcytarabine 100 mg IV days 1 3 5 Commonly used intensive consolidation schemes include intermediatehigh dose cytarabine or CPX-351 Midostaurine gemtuzumab ozogamicin daunorubicine may be added as per guidelines
Non intensive induction and consolidation schemes include azaticidine 75 mgm2 day 1-7 Venetoclax at variable dose
For the retrospective collection of samples the preceding version of ELN guidelines 2017 will be appliedThe main hypothesis of the study is that an excessive inflammasome activity in AML disrupts the balance of cytokine production leading to a clinically relevant inflammatory state which interferes with the response to chemotherapy
In two years we plan to recruit 80 adult participants with a new diagnosis of AML undergoing first line chemotherapy treatment
The protocol is a multicenter national observational study indeed it is based on the Clinical Practice and is aimed at gathering information from the biological samples collected during the diagnosis process and after a first line treatment The Study will be prospective and retrospective The total duration of enrolment will be from August 2024 to January 2026 the observation period will be up to 6 months The information about the treatment and the assessment on disease responserelapseprogression will be collected for stratification and monitoring purpose Retrospectively specimens demographical and clinical information are retrieved from AML patients previously recruited by UO1 will be utilized Prospectively new AML patients will be recruited UO1 recruits AML patients collects biological samples at diagnosis and after chemotherapy processes and biobanks specimens and conducts functional inflammasome assays gene expression analysis and immunophenotyping of AML blasts in peripheral blood and bone marrow Additionally immunohistochemistry is performed on bone marrow biopsies UO2 recruits AML patients processes and cryobank specimens and ships samples to UO1 It also produce all diagnostic data for clinical standard of AML blasts in peripheral blood and bone marrow with immunohistochemistry conducted on bone marrow biopsies
The biological samples collected for the study include bone marrow biopsies and peripheral blood
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None