GVHDAATGVHD-MARKNCT03188601
α1-antitrypsin (AAT) Levels and Functions in Allogeneic Bone Marrow Transplantation and Throughout Progression Into GVHD
An observational study of GVHD and Bone Marrow Transplant Failure, run by Rambam Health Care Campus at 4 sites in Israel.
Trial summary
Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD. PRIMARY ENDPOINT 1. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- GVHD, Bone Marrow Transplant Failure, Alpha 1-Antitrypsin
- How many people
- 27 participants
- Where
- 4 sitesIsrael
- Study dates
- 27 Jan 2018to 1 Aug 2022
- How long will I take part?
- 1 Year
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: In every medical center in which a bone marrow transplantation is performed, allogeneic transplantation recipients will be recruited for the trial.
Who may be able to join
- Candidates for allogeneic transplantation for the first time, scheduled to receive HSCT from HLA-matched sibling or an unrelated matched donor
- Signed informed consent by the donor(Healthy volunteers) and the patient
Who cannot join
- Patients undergoing immunosuppressive treatment prior to preparation for bone-marrow transplantation.
- Pregnant and disabled patients.
Trial locations and contacts
4 sites in 1 country.
Israel4 sites
Soroka Medical Center
Beersheba, South, 8410101
Rambam MC
Haifa, North, 3525408
Hadassah
Jerusalem, Center, 91120
Tel Aviv Sourasky Medical Center - Ichilov Hospital
Tel Aviv, Center, 6423906
About this study
Official title: Relative Inactivity of Alpha-1-antitrypsin After Bone Marrow Transplantation as a Dynamic Biomarker for GVHD and Prognosis: a Prospective Cohort Study
Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD.
PRIMARY ENDPOINT 1. Serum AAT levels and activity, before myeloablative preconditioning, as well as on days (-3),0,7,14,28 from HSCT and every 21 days thereafter.
SECONDARY ENDPOINTS 1. Correlation between AAT patterns and:
- Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.
- Patient survival
- Liver function tests
- GVHD grade: skin manifestations, weight, GI and liver histopathology
- Graft-versus-leukemia effect
Read the detailed description
This study will focus on each individual patient from the early point of myeloablative conditioning through HSCT and GVHD. The rationale for this individualized approach is to account for the anticipated variability in patient age and primary disease, background pathology and individual therapeutic course, considering the enormous heterogeneity of this condition. To compensate for this limitation, we intend to create an individualized algorithm, based on a novel dynamic biomarker, i.e., AAT functionality, individualized per patient and placed on a timeline, with the aim of minimizing future occurrences of GVHD, and by using readily available laboratory measurements. The study is designed around patient sample collection, there is no change in standard of care, therefore there is no intervention as well.
Three types of sample tubes will be collected per indicated time point:
- Serum tube for protein levels and enzymatic activity assays.
- EDTA tube for isolation of peripheral blood mononuclear cells (PBMCs), cells will be stimulated and then analyzed by FACS and lysed for RT-PCR
- EDTA tube for whole blood stimulation assay for further FACS analysis and cytokine production measurement.
After donor and recipient informed consent forms were signed, a single blood sample should be obtained from the donor on the day of transplant extraction. Time points for recipient's samples include the day of myeloablation and again immediately prior to HSCT (set as day 0 and possibly -3 in MUDs). Serum and lysed blood samples will be collected on days 7, 14, 28, and every 21 days thereafter, through the development and progression of GVHD (where relevant). Blood samples for FACS will be collected by days 0 and 28. Sample collection is planned to end within 1 year from HSCT, or two months after appearance of symptoms of GVHD, or two months after a change is introduced in the immunosuppressive therapy.
- Conditions
- GVHD, Bone Marrow Transplant Failure, Alpha 1-Antitrypsin
- Keywords
- Graft vs Host Disease, Immune System Diseases, Protease Inhibitors, Alpha 1-Antitrypsin, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Trypsin Inhibitors, Serine Proteinase Inhibitors
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Graft vs Host Disease, Immune System Diseases
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 |
|---|---|---|
| Rambam | Approximately 40 patients in total.No intervention planned. | |
| Soroka | Approximately 10 patients in total.No intervention planned. | |
| Tel Aviv Souraski | Approximately 40 patients in total.No intervention planned. | |
| Jerusalem Hadassah | Approximately 50 patients in total. No intervention planned. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients progressing into acute or chronic GVHD
Evaluation of patient circulating alpha-1-antitrypsin levels and enzymatic functions as a bio-marker for GVHD progression and grading
Measured: Up to 1 year
Secondary outcomes (1)
Correlation between AAT pattern and survivability, response to immunosuppressive treatment. liver functions, immunocyte activities.
Correlation between AAT patterns and:
- Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.
- Patient survival
- Liver function tests
- GVHD grade: skin manifestations, weight, GI and liver histopathology
- Graft-versus-leukemia effect
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2017
- Study start27 Jan 2018
- Primary completion1 Feb 2022
- Study completion1 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GVHDStudies of the same condition, open and under way.
- 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
- 27 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Soroka University Medical Center, Tel-Aviv Sourasky Medical Center, Hadassah Medical Organization
- Responsible party
- Sponsor
- Investigators
- Eli Lewis, Professor, Principal investigator, Ben-Gurion University of the Negev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03188601
- Sponsor's protocol ID
- 0196-17-RMB
- Other IDs
- A1373
- Acronym
- AATGVHD-MARK
- Status last verified
- Apr 2023
- First submitted
- 13 Jun 2017
- Last updated
- 4 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The clinical individual participant data will be further analyzed by other researchers after the study is completed.That is in order to combine this clinical data with other experiments' results. no
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Inactivity of Alpha-1-antitrypsin After Bone Marrow Transplantation as a Dynamic Biomarker for GVHD and Prognosis: a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT03188601
- Acronym / sponsor ID
- AATGVHD-MARK / 0196-17-RMB
- Conditions
- GVHD, Bone Marrow Transplant Failure, Alpha 1-Antitrypsin
- Keywords
- Graft vs Host Disease, Immune System Diseases, Protease Inhibitors, Alpha 1-Antitrypsin, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Trypsin Inhibitors, Serine Proteinase Inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- Soroka University Medical Center, Tel-Aviv Sourasky Medical Center, Hadassah Medical Organization
- Study start
- 27 Jan 2018 (actual)
- Primary completion
- 1 Feb 2022 (actual)
- Study completion
- 1 Aug 2022 (actual)
- First posted
- 15 Jun 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.
Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD.
PRIMARY ENDPOINT 1. Serum AAT levels and activity, before myeloablative preconditioning, as well as on days (-3),0,7,14,28 from HSCT and every 21 days thereafter.
SECONDARY ENDPOINTS 1. Correlation between AAT patterns and:
- Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.
- Patient survival
- Liver function tests
- GVHD grade: skin manifestations, weight, GI and liver histopathology
- Graft-versus-leukemia effect
Detailed description
This study will focus on each individual patient from the early point of myeloablative conditioning through HSCT and GVHD. The rationale for this individualized approach is to account for the anticipated variability in patient age and primary disease, background pathology and individual therapeutic course, considering the enormous heterogeneity of this condition. To compensate for this limitation, we intend to create an individualized algorithm, based on a novel dynamic biomarker, i.e., AAT functionality, individualized per patient and placed on a timeline, with the aim of minimizing future occurrences of GVHD, and by using readily available laboratory measurements. The study is designed around patient sample collection, there is no change in standard of care, therefore there is no intervention as well.
Three types of sample tubes will be collected per indicated time point:
- Serum tube for protein levels and enzymatic activity assays.
- EDTA tube for isolation of peripheral blood mononuclear cells (PBMCs), cells will be stimulated and then analyzed by FACS and lysed for RT-PCR
- EDTA tube for whole blood stimulation assay for further FACS analysis and cytokine production measurement.
After donor and recipient informed consent forms were signed, a single blood sample should be obtained from the donor on the day of transplant extraction. Time points for recipient's samples include the day of myeloablation and again immediately prior to HSCT (set as day 0 and possibly -3 in MUDs). Serum and lysed blood samples will be collected on days 7, 14, 28, and every 21 days thereafter, through the development and progression of GVHD (where relevant). Blood samples for FACS will be collected by days 0 and 28. Sample collection is planned to end within 1 year from HSCT, or two months after appearance of symptoms of GVHD, or two months after a change is introduced in the immunosuppressive therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Rambam | – | –Approximately 40 patients in total.No intervention planned. |
| Soroka | – | –Approximately 10 patients in total.No intervention planned. |
| Tel Aviv Souraski | – | –Approximately 40 patients in total.No intervention planned. |
| Jerusalem Hadassah | – | –Approximately 50 patients in total. No intervention planned. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- In every medical center in which a bone marrow transplantation is performed, allogeneic transplantation recipients will be recruited for the trial.
Key inclusion criteria (2 listed)
- Candidates for allogeneic transplantation for the first time, scheduled to receive HSCT from HLA-matched sibling or an unrelated matched donor
- Signed informed consent by the donor(Healthy volunteers) and the patient
Key exclusion criteria (2 listed)
- Patients undergoing immunosuppressive treatment prior to preparation for bone-marrow transplantation.
- Pregnant and disabled patients.
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
Number of patients progressing into acute or chronic GVHD
Time frame: Up to 1 year
Evaluation of patient circulating alpha-1-antitrypsin levels and enzymatic functions as a bio-marker for GVHD progression and grading
1 secondary outcome
Correlation between AAT pattern and survivability, response to immunosuppressive treatment. liver functions, immunocyte activities.
Time frame: Up to 1 year
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 4 Apr 2023.
- Individual participant dataSharing planned: Yes. The clinical individual participant data will be further analyzed by other researchers after the study is completed.That is in order to combine this clinical data with other experiments' results. no
Related trials for GVHD
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Ex Vivo-Expanded Regulatory T Cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic GVHD
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Trial of 2 Step ATG for Prevention of Acute GVHD Post Allogeneic Stem Cell Transplant
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Chronic Granulomatous Disease
RecruitingObservational study
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Graft-versus-leukemia, Graft vs Host Disease
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.
Eli Lewis, Professor principal investigator
Ben-Gurion University of the Negev
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of GVHD and Bone Marrow Transplant Failure, run by Rambam Health Care Campus at 4 sites in Israel.
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 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: finished, as of the sponsor's last update on 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Israel. 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?
Number of patients progressing into acute or chronic GVHD (time frame: Up to 1 year). 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 4 Apr 2023.