Myelodysplastic SyndromesBMP-MDSNCT06175923
Role of BMP Pathway in MDS Progression
An observational study of Myelodysplastic Syndromes and Acute Myelogenous Leukemia, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Myelodysplastic syndromes (MDS) are hematological cancers that can progress to acute myelogenous leukemia (AML). The involvement of the microenvironment in the maintenance, resistance and evolution of MDS is increasingly described. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Acute Myelogenous Leukemia
- What is being tested?
- Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 27 Jan 2024to 27 Jan 2034
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Adult patients with untreated myelodysplastic syndromes at risk of progression to acute myeloid leukemia. * Adult patients with de novo AML
Who may be able to join
- Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization Or
- Adult patient with suspicion of de novo acute myeloid leukemia at initial treatment
Who cannot join
- Frontier MDS/myeloproliferative syndromes including chronic myelomonocytic leukemia
- MDS and AML having already benefited from cytotoxic treatment including hydroxycarbamide, azacytidine, intensive chemotherapy
- Patients objecting to their inclusion in the study
- Pregnant or breastfeeding women
- Patients under legal protection measure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Role of the BMP Pathway in Myelodysplastic Syndromes Progression and in the Transition to Acute Myeloid Leukemia
Myelodysplastic syndromes (MDS) are hematological cancers that can progress to acute myelogenous leukemia (AML). The involvement of the microenvironment in the maintenance, resistance and evolution of MDS is increasingly described.
The Bone Morphogenetic Protein (BMP) pathway is involved in numerous functions, including self-renewal of the hematopoietic stem cell compartment and the regulation of hematopoiesis, via interaction with bone marrow stromal cells. Investigators have demonstrated its involvement in chronic myeloid leukemia (CML) and AML, in particular via the activation of TWIST1, ΔNp73, NANOG; it is responsible for an increased state of quiescence of certain cancer stem cells and their resistance.
Read more
Preliminary results based on the analysis of large databases suggest that the BMP pathway is also altered early in MDS. This study explores the alteration of this pathway in MDS and its involvement in the transformation into AML.
If appropriate, the BMP pathway could constitute a very promising therapeutic target to combat transformation into AML.
- Being tested
- Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care
- Keywords
- BMP, MSC, MDS, microenvironment
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine careBiological
When bone marrow is collected as part of a patient's care (diagnosis, follow-up, suspected AML/MDS hemopathy), one or two additional EDTA tubes of marrow are collected. Certain hematological data (NFP, genetic and molecular characteristics) will be collected in anonymized form and correlated with the BMP pathway alterations measured.
| Study group | Role | What they receive |
|---|---|---|
| MDS patients | Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization:
* one or more cytopenias,
* and/or dysplasia of one or more lines,
* and/or bone marrow blastosis
* and/or sideroblasts in medullary crowns
* and/or genetic/cytogenetic abnormalities characteristic of MDS.
* Whatever the R-IPSS stage (Revised International Prognostic Scoring System)
* No history of cytotoxic treatment (hydroxycarbamide, azacytidine) Receives: Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care | |
| AML patients | Adult patients with suspected de novo acute myeloid leukemia at initial management Receives: Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels :
Marrow plasma to study the concentration of cytokines of interest BMP2 and BMP4
Measured: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels :
Medullary blood mononuclear cells: expression of membrane receptors BMPRIA and BMPRIB by RT-QPCR and flow cytometry, expression of cytokines BMP2 and BMP4 (RT-QPCR), degree of phosphorylation of SMAD intermediates by western blot and/or flow cytometry, expression of BMP pathway target genes by RT-QPCR
Measured: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at functional level :
Medullary MSCs will be cultured and studied from functional angle (culture, colony-forming units tests, long term culture initiating colony)
Measured: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at transcriptomic level :
Medullary MSCs will be cultured and studied from transcriptomic angle (expression of receptors, BMP cytokines, target genes, etc.).
Measured: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein level :
Medullary MSCs will be cultured and studied from protein angle (cytokines present in the supernatant).
Measured: at diagnosis, at 6 months, at 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2023
- Study start27 Jan 2024 (estimated)
- Primary completion27 Jan 2029 (estimated)
- Study completion27 Jan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06175923
- Sponsor's protocol ID
- 69HCL22_0491
- Acronym
- BMP-MDS
- Status last verified
- Nov 2023
- First submitted
- 29 Nov 2023
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the BMP Pathway in Myelodysplastic Syndromes Progression and in the Transition to Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06175923
- Acronym / sponsor ID
- BMP-MDS / 69HCL22_0491
- Keywords
- BMP, MSC, MDS, microenvironment
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 27 Jan 2024 (estimated)
- Primary completion
- 27 Jan 2029 (estimated)
- Study completion
- 27 Jan 2034 (estimated)
- First posted
- 19 Dec 2023 (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.
Myelodysplastic syndromes (MDS) are hematological cancers that can progress to acute myelogenous leukemia (AML). The involvement of the microenvironment in the maintenance, resistance and evolution of MDS is increasingly described.
The Bone Morphogenetic Protein (BMP) pathway is involved in numerous functions, including self-renewal of the hematopoietic stem cell compartment and the regulation of hematopoiesis, via interaction with bone marrow stromal cells. Investigators have demonstrated its involvement in chronic myeloid leukemia (CML) and AML, in particular via the activation of TWIST1, ΔNp73, NANOG; it is responsible for an increased state of quiescence of certain cancer stem cells and their resistance.
Preliminary results based on the analysis of large databases suggest that the BMP pathway is also altered early in MDS. This study explores the alteration of this pathway in MDS and its involvement in the transformation into AML.
If appropriate, the BMP pathway could constitute a very promising therapeutic target to combat transformation into AML.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDS patients | – | Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine careAdult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization: * one or more cytopenias, * and/or dysplasia of one or more lines, * and/or bone marrow blastosis * and/or sideroblasts in medullary crowns * and/or genetic/cytogenetic abnormalities characteristic of MDS. * Whatever the R-IPSS stage (Revised International Prognostic Scoring System) * No history of cytotoxic treatment (hydroxycarbamide, azacytidine) |
| AML patients | – | Biological: Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine careAdult patients with suspected de novo acute myeloid leukemia at initial management |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Adult patients with untreated myelodysplastic syndromes at risk of progression to acute myeloid leukemia. * Adult patients with de novo AML
Key inclusion criteria (2 listed)
- Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization Or
- Adult patient with suspicion of de novo acute myeloid leukemia at initial treatment
Key exclusion criteria (5 listed)
- Frontier MDS/myeloproliferative syndromes including chronic myelomonocytic leukemia
- MDS and AML having already benefited from cytotoxic treatment including hydroxycarbamide, azacytidine, intensive chemotherapy
- Patients objecting to their inclusion in the study
- Pregnant or breastfeeding women
- Patients under legal protection measure
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 |
|---|---|---|
| Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine careWhen bone marrow is collected as part of a patient's care (diagnosis, follow-up, suspected AML/MDS hemopathy), one or two additional EDTA tubes of marrow are collected. Certain hematological data (NFP, genetic and molecular characteristics) will be collected in anonymized form and correlated with the BMP pathway alterations measured. | Biological | AML patients, MDS patients |
Primary outcome
Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels
Time frame: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels : Marrow plasma to study the concentration of cytokines of interest BMP2 and BMP4
Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction
Time frame: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein, transcriptomic and functional levels : Medullary blood mononuclear cells: expression of membrane receptors BMPRIA and BMPRIB by RT-QPCR and flow cytometry, expression of cytokines BMP2 and BMP4 (RT-QPCR), degree of phosphorylation of SMAD intermediates by western blot and/or flow cytometry, expression of BMP pathway target genes by RT-QPCR
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level
Time frame: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at functional level : Medullary MSCs will be cultured and studied from functional angle (culture, colony-forming units tests, long term culture initiating colony)
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level
Time frame: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at transcriptomic level : Medullary MSCs will be cultured and studied from transcriptomic angle (expression of receptors, BMP cytokines, target genes, etc.).
Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level
Time frame: at diagnosis, at 6 months, at 5 years
Descriptive analysis of the BMP pathway in bone marrow-derived cells from MDS patients at the protein level : Medullary MSCs will be cultured and studied from protein angle (cytokines present in the supernatant).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myelodysplastic Syndromes and Acute Myelogenous Leukemia, run by Hospices Civils de Lyon at 1 site in France.
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 5 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: opening soon, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maël MD Heiblig (0478864340 ext. +33, Mael.heiblig@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels (time frame: at diagnosis, at 6 months, at 5 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jan 2024.