Multiple MyelomaMICRO-MMNCT05712967
Role of the Host Microbiota and Il-17 in Favoring Multiple Myeloma Progression
An observational study of Multiple Myeloma, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Goal of this observational, non-interventional study is to demonstrate that in humans a correlation exists between bone marrow (BM) levels of the cytokine interleukin 17 (IL-17) and composition of the gut microbiota in patients affected by smoldering multiple myeloma (SMM) or multiple myeloma (MM). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Multiple Myeloma
- How many people
- 62 participants
- Where
- 1 siteItaly
- Study dates
- 14 Jun 2019to 5 Feb 2024
- 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 18 to 80 years
- All sexes
- Adult, Older adult
Study population: 52 patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM or MM, and 10 healthy controls older than 18 years and accepting to sign the informed consent
Who may be able to join
- patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM or MM, and 10 healthy controls older than 18 years and accepting to sign the informed consent
Who cannot join
- Non-Caucasian subjects.
- Subjects younger than 18 years.
- Subjects that did not accept to sign the informed consent.
- Subjects reporting infectious diseases requiring antibiotic therapy in the previous three months, ongoing antibiotic therapy or prophylaxis.
- Subjects who already underwent HSCT or under pharmacologic therapy for MM.
- Subjects affected by autoimmune diseases with the exception of thyroiditis.
- Subjects affected by HIV, HBV or HCV.
Trial locations and contacts
1 site in 1 country.
About this study
Goal of this observational, non-interventional study is to demonstrate that in humans a correlation exists between bone marrow (BM) levels of the cytokine interleukin 17 (IL-17) and composition of the gut microbiota in patients affected by smoldering multiple myeloma (SMM) or multiple myeloma (MM).
Enrolled SMM/MM patients will be analyzed for their bone marrow levels of IL-17 together with the distribution of T helper 17 lymphocytes in their BM and peripheral blood. These analyses will be correlated with analyses of the patients' gut microbiome to identify commensal bacteria potentially involved in Th17 cell expansion.
Read the detailed description
Each year, approximately 10% of asymptomatic smoldering multiple myeloma (SMM) patients progress to incurable multiple myeloma (MM), a neoplasm of plasma cells causing anemia, bone lesions, increased blood calcium levels and renal damage. Lack of consolidated predictive biomarkers of disease progression makes the selection of SMM candidates to early treatment difficult, and a watch and wait approach is still preferred for these patients. We have recently reported results from a retrospective clinical study showing that SMM patients with higher levels of bone marrow (BM) interleukin-17 (IL-17) were at higher risk to rapidly progress to MM than SMM patients with lower IL-17 levels. Several lines of evidence in autoimmune diseases and cancer link IL-17-producing T lymphocytes (Th17) with the gut microbiota, and evidence exists in patients affected by MM that the gut microbiota impacts disease progression and susceptibility to therapies. Such link has not been investigated in patients affected by SMM.
Goal of this observational, non-interventional study is to demonstrate that in humans a correlation exists between BM levels of IL-17 and composition of the gut microbiota.
Enrolled SMM/MM patients will be analyzed for their bone marrow levels of IL-17 together with the distribution of Th17 cells in their BM and peripheral blood. These analyses will be correlated with analyses of the patients' gut microbiome to identify commensal bacteria potentially involved in Th17 cell expansion. We will seek a direct link between gut microbiota, IL-17 and MM by transplanting mice affected by MM with stool samples from the enrolled SMM/MM patients. We expect a more aggressive disease in avatar mice transplanted with stools from IL-17-high patients when compared to IL-17-low patients. Because samples will be collected both in Italy and in the USA, the study will also allow investigating the impact of additional environmental factors (e.g. Mediterranean versus high-fat diet) on host microbiota and IL-17-driven MM. Thus, primary outcome of the study will be evidence of a correlation between BM levels of IL-17 and the composition of the gut microbiota in patients affected by SMM/MM.
The recruited patients will also be monitored for disease progression or relapse after therapy. The study has no statistical power to define correlates of disease progression in these patients. However, the gut microbiome and the levels of BM IL-17 in SMM patients will be correlated to time to MM progression. Additionally, microbiome and BM IL-17 levels in MM patients eligible for hematopoietic stem cell transplantation (HSCT) will be correlated with response to the induction phase, which is routinely evaluated within 3 months. We expect better responses in patients with low levels of BM IL-17. Additionally, based on recently published experience on the role of enteric microbiome in influencing the HSCT outcomes, we have begun collecting stool samples from MM patients before and after HSCT. Therefore, once we identify patients with early relapse, we will be able to determine if they were colonized with tumor-promoting commensal bacteria following the transplant.
- Conditions
- Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PATIENTS WITH MM | patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for MM | |
| PATIENTS WITH sMM | patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM | |
| Controls | healthy controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
the role of microbiota and IL17 in MM
This study will provide direct evidence that the human gut microbiota modulate BM Th17 cells and MM progression . It will also provide the ground for a larger prospective clinical study on the predictive value of BM IL-17 in SMM patients.
Measured: 5YRS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2023
- Study start14 Jun 2019
- Primary completion5 Feb 2024
- Study completion5 Feb 2024
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 Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matteo Bellone, MD, IRCCS San Raffaele
- Investigators
- matteo bellone, md, Principal investigator, IRCCS Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05712967
- Sponsor's protocol ID
- Observational study
- Acronym
- MICRO-MM
- Status last verified
- Feb 2024
- First submitted
- 23 Dec 2022
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Anderson KC, Carrasco RD. Pathogenesis of myeloma. Annu Rev Pathol. 2011;6:249-74. doi: 10.1146/annurev-pathol-011110-130249.
PubMed 21261519Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, Rajkumar SV. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018 Jan 18;378(3):241-249. doi: 10.1056/NEJMoa1709974.
PubMed 29342381Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015 May 14;125(20):3069-75. doi: 10.1182/blood-2014-09-568899. Epub 2015 Apr 2.
PubMed 25838344Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010.
PubMed 26181891
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Host Microbiota and Il-17 in Favoring Multiple Myeloma Progression
- ClinicalTrials.gov ID
- NCT05712967
- Acronym / sponsor ID
- MICRO-MM / Observational study
- Conditions
- Multiple Myeloma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 14 Jun 2019 (actual)
- Primary completion
- 5 Feb 2024 (actual)
- Study completion
- 5 Feb 2024 (actual)
- First posted
- 6 Feb 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.
Goal of this observational, non-interventional study is to demonstrate that in humans a correlation exists between bone marrow (BM) levels of the cytokine interleukin 17 (IL-17) and composition of the gut microbiota in patients affected by smoldering multiple myeloma (SMM) or multiple myeloma (MM).
Enrolled SMM/MM patients will be analyzed for their bone marrow levels of IL-17 together with the distribution of T helper 17 lymphocytes in their BM and peripheral blood. These analyses will be correlated with analyses of the patients' gut microbiome to identify commensal bacteria potentially involved in Th17 cell expansion.
Detailed description
Each year, approximately 10% of asymptomatic smoldering multiple myeloma (SMM) patients progress to incurable multiple myeloma (MM), a neoplasm of plasma cells causing anemia, bone lesions, increased blood calcium levels and renal damage. Lack of consolidated predictive biomarkers of disease progression makes the selection of SMM candidates to early treatment difficult, and a watch and wait approach is still preferred for these patients. We have recently reported results from a retrospective clinical study showing that SMM patients with higher levels of bone marrow (BM) interleukin-17 (IL-17) were at higher risk to rapidly progress to MM than SMM patients with lower IL-17 levels. Several lines of evidence in autoimmune diseases and cancer link IL-17-producing T lymphocytes (Th17) with the gut microbiota, and evidence exists in patients affected by MM that the gut microbiota impacts disease progression and susceptibility to therapies. Such link has not been investigated in patients affected by SMM.
Goal of this observational, non-interventional study is to demonstrate that in humans a correlation exists between BM levels of IL-17 and composition of the gut microbiota.
Enrolled SMM/MM patients will be analyzed for their bone marrow levels of IL-17 together with the distribution of Th17 cells in their BM and peripheral blood. These analyses will be correlated with analyses of the patients' gut microbiome to identify commensal bacteria potentially involved in Th17 cell expansion. We will seek a direct link between gut microbiota, IL-17 and MM by transplanting mice affected by MM with stool samples from the enrolled SMM/MM patients. We expect a more aggressive disease in avatar mice transplanted with stools from IL-17-high patients when compared to IL-17-low patients. Because samples will be collected both in Italy and in the USA, the study will also allow investigating the impact of additional environmental factors (e.g. Mediterranean versus high-fat diet) on host microbiota and IL-17-driven MM. Thus, primary outcome of the study will be evidence of a correlation between BM levels of IL-17 and the composition of the gut microbiota in patients affected by SMM/MM.
The recruited patients will also be monitored for disease progression or relapse after therapy. The study has no statistical power to define correlates of disease progression in these patients. However, the gut microbiome and the levels of BM IL-17 in SMM patients will be correlated to time to MM progression. Additionally, microbiome and BM IL-17 levels in MM patients eligible for hematopoietic stem cell transplantation (HSCT) will be correlated with response to the induction phase, which is routinely evaluated within 3 months. We expect better responses in patients with low levels of BM IL-17. Additionally, based on recently published experience on the role of enteric microbiome in influencing the HSCT outcomes, we have begun collecting stool samples from MM patients before and after HSCT. Therefore, once we identify patients with early relapse, we will be able to determine if they were colonized with tumor-promoting commensal bacteria following the transplant.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PATIENTS WITH MM | – | –patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for MM |
| PATIENTS WITH sMM | – | –patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM |
| Controls | – | –healthy controls |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 52 patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM or MM, and 10 healthy controls older than 18 years and accepting to sign the informed consent
Key inclusion criteria (1 listed)
- patients fulfilling the International Myeloma Working Group (IMWG) diagnostic criteria for SMM or MM, and 10 healthy controls older than 18 years and accepting to sign the informed consent
Key exclusion criteria (7 listed)
- Non-Caucasian subjects.
- Subjects younger than 18 years.
- Subjects that did not accept to sign the informed consent.
- Subjects reporting infectious diseases requiring antibiotic therapy in the previous three months, ongoing antibiotic therapy or prophylaxis.
- Subjects who already underwent HSCT or under pharmacologic therapy for MM.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
the role of microbiota and IL17 in MM
Time frame: 5YRS
This study will provide direct evidence that the human gut microbiota modulate BM Th17 cells and MM progression . It will also provide the ground for a larger prospective clinical study on the predictive value of BM IL-17 in SMM patients.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Background: PubMed 21261519Anderson KC, Carrasco RD. Pathogenesis of myeloma. Annu Rev Pathol. 2011;6:249-74. doi: 10.1146/annurev-pathol-011110-130249.
- Background: PubMed 29342381Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, Rajkumar SV. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018 Jan 18;378(3):241-249. doi: 10.1056/NEJMoa1709974.
- Background: PubMed 25838344Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015 May 14;125(20):3069-75. doi: 10.1182/blood-2014-09-568899. Epub 2015 Apr 2.
- Background: PubMed 26181891Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010.
- Individual participant dataSharing planned: Undecided
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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.
matteo bellone, md principal investigator
IRCCS Ospedale San Raffaele
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 Multiple Myeloma, run by IRCCS San Raffaele at 1 site in Italy.
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 7 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: finished, as of the sponsor's last update on 1 Mar 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the role of microbiota and IL17 in MM (time frame: 5YRS). 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 NCT05712967, 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 1 Mar 2024.