Relapse LeukemiaEVADENCT03964922
Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation
A study testing blood sample and bone marrow sample in people with Relapse Leukemia and Allogeneic Stem Cell Transplantation, run by Central Hospital, Nancy, France.
Trial summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only treatment available to cure acute myeloid leukemia and high risk myelodysplasia. Allo-HSCT has an anti-tumor effect (called the graft versus leukemia effect= GVL) mediated by donor lymphocytes. Read more about this study
- Who is it for?
- Ages 18 to 71 years
- Conditions the study is for
- Relapse Leukemia, Allogeneic Stem Cell Transplantation, Immune Evasion, Tumor
- What is being tested?
- blood sample and bone marrow sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2019to 1 Nov 2022
- Phase
- Interventional
- 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 71 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute myeloid leukemia in complete cytological remission with intermediate or high risk prognosis according to ELN 2017
- Patients with myelodysplasia according to the WHO 2016 definition, with IPSS ≥1.5 and disease status is : stable or in partial response or complete response according to IWG 2006.
- Patients with indication of first allo-HSCT with a matched related or unrelated donor
- Patients receiving non-myeloablative or reduced toxicity conditioning
- Patients affiliated to a social security scheme
- Patients who have received a complete information on the organization of the research and signed his informed consent
Who cannot join
- Patients with an alternative donor (HLA 5/10 or unit cord blood)
- Patients with another active cancer or a history of cancer diagnosed in the previous 5 years
- Patients with uncontrolled infection at the time of inclusion, or with positive HIV (1 + 2) or HTLV (1 + 2), Hepatitis C or active hepatitis B
- Patients referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only treatment available to cure acute myeloid leukemia and high risk myelodysplasia. Allo-HSCT has an anti-tumor effect (called the graft versus leukemia effect= GVL) mediated by donor lymphocytes. This GVL effect is often associated with graft-versus-host disease (GVHD). Several studies have shown that the relapse incidence is lower in patients developing chronic GVHD. These studies confirm the impact of donor immune system on leukemic residual cells. In fact, the relapse incidence increased in patients with no sign of GVHD. The investigators assume that leukemic cells probably use mechanisms to inhibit the allogeneic response. These escape mechanisms to immunosurveillance have been described in other malignancies. Out of context of the allo-HSCT, in acute myeloid leukemias and myelodysplasia, correlations between the severity of the disease and the presence of regulatory T cells (Tregs) or exhausted T cells (PD1 positive) in the bone marrow and in the blood of patients were described at the time of diagnosis or relapse. Myeloid Derived Suppressive Cells (MDSCs) have been described as capable of inducing Tregs and exhausted T cells in the tumor microenvironment.The investigators want to evaluate the role of myeloid suppressive cells in bone marrow after allo HSCT. They hypothesize that their presence in bone marrow and / or blood recipient is correlated to the relapse incidence.
- Being tested
- blood sample, bone marrow sample
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleBiological
20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT
bone marrow sampleBiological
3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT
| Study group | Role | What they receive |
|---|---|---|
| immune escape mecanims | Experimental | Cohort study with a representative sample of patients Receives: Biological: blood sample; Biological: bone marrow sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myeloid suppressive cells and relapse incidence
To investigate the relationship between the percentage of myeloid derived suppressive cells (MDSCs) in total leukocytes in peripheral blood and the relapse incidence after allogeneic stem cell transplantation.
The patients will be grouped according to median MDSC frequency values. Relapse incidence will be compared across the two groups (low and high frequency of MDSC).
Measured: 2 years
Secondary outcomes (4)
Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells)
To correlate levels of bone marrow MDSC and regulatory T cells (Tregs) and exhausted T cells and the quality of mesenchymal cells in bone marrow.
Measured: 2 years
percentage of myeloid suppressive cells
Measured: 2 years
incidence of acute GVHD
Measured: 2 years
incidence of chronic GVHD
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2019
- Study start1 Sep 2019 (estimated)
- Primary completion30 Jun 2022 (estimated)
- Study completion1 Nov 2022 (estimated)
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 Relapse LeukemiaStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03964922
- Sponsor's protocol ID
- 2019-A00842-55
- Acronym
- EVADE
- Status last verified
- May 2019
- First submitted
- 3 May 2019
- Last updated
- 28 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prevot O, Garfa-Traore M, Suarez F, Trebeden-Negre H, Mohty M, Bennett CL, Chakraverty R, Hermine O, Rubio MT. G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci Transl Med. 2015 Apr 1;7(281):281ra42. doi: 10.1126/scitranslmed.3010435.
PubMed 25834108Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, McDonald T, Lin A, Kumar AR, DiGiusto DL, Stein AS, Pullarkat VA, Hui SK, Carlesso N, Kuo YH, Bhatia R, Marcucci G, Chen CC. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 2018 Mar;32(3):575-587. doi: 10.1038/leu.2017.259. Epub 2017 Aug 17.
PubMed 28816238Nadal E, Garin M, Kaeda J, Apperley J, Lechler R, Dazzi F. Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2007 Mar;21(3):472-9. doi: 10.1038/sj.leu.2404522. Epub 2007 Jan 11.
PubMed 17215853Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, Zeng H, Schell TD, Zheng H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015 Jul 31;5(7):e330. doi: 10.1038/bcj.2015.58.
PubMed 26230954
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03964922
- Acronym / sponsor ID
- EVADE / 2019-A00842-55
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 1 Sep 2019 (estimated)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 28 May 2019 (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.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only treatment available to cure acute myeloid leukemia and high risk myelodysplasia. Allo-HSCT has an anti-tumor effect (called the graft versus leukemia effect= GVL) mediated by donor lymphocytes. This GVL effect is often associated with graft-versus-host disease (GVHD). Several studies have shown that the relapse incidence is lower in patients developing chronic GVHD. These studies confirm the impact of donor immune system on leukemic residual cells. In fact, the relapse incidence increased in patients with no sign of GVHD. The investigators assume that leukemic cells probably use mechanisms to inhibit the allogeneic response. These escape mechanisms to immunosurveillance have been described in other malignancies. Out of context of the allo-HSCT, in acute myeloid leukemias and myelodysplasia, correlations between the severity of the disease and the presence of regulatory T cells (Tregs) or exhausted T cells (PD1 positive) in the bone marrow and in the blood of patients were described at the time of diagnosis or relapse. Myeloid Derived Suppressive Cells (MDSCs) have been described as capable of inducing Tregs and exhausted T cells in the tumor microenvironment.The investigators want to evaluate the role of myeloid suppressive cells in bone marrow after allo HSCT. They hypothesize that their presence in bone marrow and / or blood recipient is correlated to the relapse incidence.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| immune escape mecanims | Experimental | Biological: blood sample, Biological: bone marrow sampleCohort study with a representative sample of patients |
Who may qualify
- Ages
- 18 to 71 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with acute myeloid leukemia in complete cytological remission with intermediate or high risk prognosis according to ELN 2017
- Patients with myelodysplasia according to the WHO 2016 definition, with IPSS ≥1.5 and disease status is : stable or in partial response or complete response according to IWG 2006.
- Patients with indication of first allo-HSCT with a matched related or unrelated donor
- Patients receiving non-myeloablative or reduced toxicity conditioning
- Patients affiliated to a social security scheme
Key exclusion criteria (4 listed)
- Patients with an alternative donor (HLA 5/10 or unit cord blood)
- Patients with another active cancer or a history of cancer diagnosed in the previous 5 years
- Patients with uncontrolled infection at the time of inclusion, or with positive HIV (1 + 2) or HTLV (1 + 2), Hepatitis C or active hepatitis B
- Patients referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code.
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 |
|---|---|---|
| blood sample20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT | Biological | immune escape mecanims |
| bone marrow sample3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT | Biological | immune escape mecanims |
Primary outcome
Myeloid suppressive cells and relapse incidence
Time frame: 2 years
To investigate the relationship between the percentage of myeloid derived suppressive cells (MDSCs) in total leukocytes in peripheral blood and the relapse incidence after allogeneic stem cell transplantation. The patients will be grouped according to median MDSC frequency values. Relapse incidence will be compared across the two groups (low and high frequency of MDSC).
4 secondary outcomes
Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells)
Time frame: 2 years
percentage of myeloid suppressive cells
Time frame: 2 years
incidence of acute GVHD
Time frame: 2 years
incidence of chronic GVHD
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2019.
- Background: PubMed 25834108D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prevot O, Garfa-Traore M, Suarez F, Trebeden-Negre H, Mohty M, Bennett CL, Chakraverty R, Hermine O, Rubio MT. G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci Transl Med. 2015 Apr 1;7(281):281ra42. doi: 10.1126/scitranslmed.3010435.
- Background: PubMed 28816238Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, McDonald T, Lin A, Kumar AR, DiGiusto DL, Stein AS, Pullarkat VA, Hui SK, Carlesso N, Kuo YH, Bhatia R, Marcucci G, Chen CC. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 2018 Mar;32(3):575-587. doi: 10.1038/leu.2017.259. Epub 2017 Aug 17.
- Background: PubMed 17215853Nadal E, Garin M, Kaeda J, Apperley J, Lechler R, Dazzi F. Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2007 Mar;21(3):472-9. doi: 10.1038/sj.leu.2404522. Epub 2007 Jan 11.
- Background: PubMed 26230954Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, Zeng H, Schell TD, Zheng H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015 Jul 31;5(7):e330. doi: 10.1038/bcj.2015.58.
Related trials for Relapse Leukemia
RecruitingPhase 2/3
A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
B-cell Acute Lymphoblastic Leukemia
RecruitingObservational study
A Long-term Follow-up Study of Patients With ARD103 CAR-T Cell Therapies
Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, in Relapsed or Refractory
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
RecruitingObservational study
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
Hematologic Malignancy, 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?
A study testing blood sample and bone marrow sample in people with Relapse Leukemia and Allogeneic Stem Cell Transplantation, run by Central Hospital, Nancy, 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 6 inclusion and 4 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 28 May 2019. 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 Maud D'AVENI, MD (+33383153289, m.daveni-piney@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myeloid suppressive cells and relapse incidence (time frame: 2 years). 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 NCT03964922, 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 28 May 2019.