Acute Myeloid LeukemiaNCT02842112
Higher Percentage of CD34+ CD38- Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predicts Unsustained Complete Remission in Acute Myeloid Leukemia
An observational study of Acute Myeloid Leukemia, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Over recent decades, improvements have been made in the treatment of adult acute myeloid leukemia (AML). This has been mainly attributed to improvements in supportive therapy and to intensification of treatment strategies. Read more about this study
- Who is it for?
- Ages 25 to 72 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- PBSC mobilization and leukapheresis
- Type of treatment
- Injection or infusion
- How many people
- 123 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2013to May 2014
- 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 25 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome MDS or therapy-related AML) and achieving first CR after induction or salvage therapy. Three populations of CD34+ cells were distinguished based on differential expression of the CD34 and CD38 antigens
Who may be able to join
- Age ≥ 18 years
- With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome (MDS) or therapy-related AML)
- Patients achieving first CR after induction or salvage therapy
Who cannot join
- Patients with acute promyelocytic leukemia (APL)
- Concomitant uncontrolled infection, organ dysfunction or medical disease
- left ventricular ejection fraction (LVEF) < 45% as assessed by echocardiography
Trial locations and contacts
1 site in 1 country.
France1 site
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet
Pierre-Bénite, 69310
About this study
Over recent decades, improvements have been made in the treatment of adult acute myeloid leukemia (AML). This has been mainly attributed to improvements in supportive therapy and to intensification of treatment strategies. The introduction of a post-induction myeloablative regimen followed by allogeneic stem cell transplant (SCT) has reduced the relapse rate in younger adults. However, this procedure is limited by the availability of human leukocyte antigen (HLA)-identical donors and conventional SCT preparative regimens according to patient age. In the absence of a compatible donor, myeloablative chemotherapy followed by autologous peripheral blood (PB) SCT remains one treatment strategy in adult patients with AML, allowing 35 - 50% long-term survivors. Despite several advantages of the CD34+ cell mobilization procedure, recent data have shown that relapse was higher and leukemia-free survival (LFS) shorter compared with bone marrow (BM) autografts. Higher doses of CD34+ peripheral blood stem cells (PBSCs) are collected to ensure engraftment and possibly reduce the incidence of treatment-related mortality (TRM). Although there is a threshold CD34+ cell dose below which engraftment is delayed in AML, the positive linear correlation of the number of CD34+ cells and kinetics of engraftment reaches a limit above which an increase in the number of progenitor cells does not provide any additional benefit. Relapse has been shown to be higher and survival shorter for those who receive the highest CD34+ PB doses. Although highly active against the leukemia bulk, intensive chemotherapy often spares the hardiest leukemia stem cells (LSCs) responsible for relapse. Detection of minimal residual disease (MRD) in autologous PBSC products may reflect inadequate in vivo purging, at least in part responsible for relapse. Although representing a heterogeneous cell population including both normal and leukemia cells, and despite that recent data have challenged the CD34+ CD38- phenotype of LSCs in AML, the CD34+ CD38- cell population generally remains considered enriched for LSCs.
In this setting, MRD remaining during morphological complete remission (CR) should be relatively enriched in CD34+ CD38- leukemia cells, and their persistence after CR achievement should correlate with disease recurrence. This was investigated in a cohort of 123 patients with AML following apheresis procedures after CR achievement. The investigators also studied the impact of the infused dose of subpopulations of CD34+ PB cells on the outcome of a subset of 71 patients who further underwent autologous PBSCT.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- PBSC mobilization and leukapheresis
- Keywords
- Acute myeloid leukemia, prognosis, stem cell harvest, autologous transplant, leukemia stem cell
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBSC mobilization and leukapheresisOther
Mobilization and harvest of autologous PBSCs was scheduled during the recovery phase after the consolidation course. Granulocyte colony stimulating factor (G-CSF) (150 µg/m2/day) was given by daily subcutaneous injection from day 20 of the chemotherapy course until completion of the blood stem cell collections. PBSC collections were performed on 1 - 5 consecutive days during the hematopoietic recovery phase, as soon as the leukocyte count exceeded 2x 109/L.
Collections were performed after induction or after consolidation. In cases in which the minimum number of CD34+ cells was not collected, an additional mobilization was performed in steady state.
Harvesting was performed using continuous flow blood cell separators. Cells were stored in liquid nitrogen until use, according to standard techniques.
| Study group | Role | What they receive |
|---|---|---|
| CD34+ CD38- | A first cell population, which expressed the CD34 antigen and lacked CD38 (CD34+ CD38-), and often contained very few events requiring to be tightly clustered in a forward light scatter /side light scatter (FSC/ SSC) and CD45/SSC plot; Receives: Other: PBSC mobilization and leukapheresis | |
| CD34+ CD38low | A second population characterized by expression of the CD34 antigen and by a low density of CD38 antigen (CD34+ CD38low) Receives: Other: PBSC mobilization and leukapheresis | |
| CD34+ CD38+ | A third population characterized by a large density of CD38 and CD34 antigens (CD34+ CD38+). Antigens were expressed as percent positively stained cells as well as intensity of the fluorescence signal quantified as mean fluorescence intensity (MFI) from CD34+ gated cells and from CD45low/SSC total immature cells Receives: Other: PBSC mobilization and leukapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
EFS was defined from date of first apheresis to the date of relapse or death, or last contact with the patient in continuous complete remission
Measured: During the study (1 year)
Secondary outcomes (1)
Overall survival (OS)
OS was defined as the time from first apheresis to death or last patient contact. For patients effectively autografted, OS and EFS were calculated from the date of autologous SCT
Measured: During the study (1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startJan 2013
- Primary completionDec 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies 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
- Retrospective
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xavier THOMAS, MD-PhD, Principal investigator, Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02842112
- Sponsor's protocol ID
- 69HCL16_0460
- Status last verified
- Jul 2016
- First submitted
- 20 Jul 2016
- Last updated
- 25 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Higher Percentage of CD34+ CD38- Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predicts Unsustained Complete Remission in Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02842112
- Acronym / sponsor ID
- 69HCL16_0460
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute myeloid leukemia, prognosis, stem cell harvest, autologous transplant, leukemia stem cell
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 22 Jul 2016 (estimated)
- 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.
Over recent decades, improvements have been made in the treatment of adult acute myeloid leukemia (AML). This has been mainly attributed to improvements in supportive therapy and to intensification of treatment strategies. The introduction of a post-induction myeloablative regimen followed by allogeneic stem cell transplant (SCT) has reduced the relapse rate in younger adults. However, this procedure is limited by the availability of human leukocyte antigen (HLA)-identical donors and conventional SCT preparative regimens according to patient age. In the absence of a compatible donor, myeloablative chemotherapy followed by autologous peripheral blood (PB) SCT remains one treatment strategy in adult patients with AML, allowing 35 - 50% long-term survivors. Despite several advantages of the CD34+ cell mobilization procedure, recent data have shown that relapse was higher and leukemia-free survival (LFS) shorter compared with bone marrow (BM) autografts. Higher doses of CD34+ peripheral blood stem cells (PBSCs) are collected to ensure engraftment and possibly reduce the incidence of treatment-related mortality (TRM). Although there is a threshold CD34+ cell dose below which engraftment is delayed in AML, the positive linear correlation of the number of CD34+ cells and kinetics of engraftment reaches a limit above which an increase in the number of progenitor cells does not provide any additional benefit. Relapse has been shown to be higher and survival shorter for those who receive the highest CD34+ PB doses. Although highly active against the leukemia bulk, intensive chemotherapy often spares the hardiest leukemia stem cells (LSCs) responsible for relapse. Detection of minimal residual disease (MRD) in autologous PBSC products may reflect inadequate in vivo purging, at least in part responsible for relapse. Although representing a heterogeneous cell population including both normal and leukemia cells, and despite that recent data have challenged the CD34+ CD38- phenotype of LSCs in AML, the CD34+ CD38- cell population generally remains considered enriched for LSCs.
In this setting, MRD remaining during morphological complete remission (CR) should be relatively enriched in CD34+ CD38- leukemia cells, and their persistence after CR achievement should correlate with disease recurrence. This was investigated in a cohort of 123 patients with AML following apheresis procedures after CR achievement. The investigators also studied the impact of the infused dose of subpopulations of CD34+ PB cells on the outcome of a subset of 71 patients who further underwent autologous PBSCT.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CD34+ CD38- | – | Other: PBSC mobilization and leukapheresisA first cell population, which expressed the CD34 antigen and lacked CD38 (CD34+ CD38-), and often contained very few events requiring to be tightly clustered in a forward light scatter /side light scatter (FSC/ SSC) and CD45/SSC plot; |
| CD34+ CD38low | – | Other: PBSC mobilization and leukapheresisA second population characterized by expression of the CD34 antigen and by a low density of CD38 antigen (CD34+ CD38low) |
| CD34+ CD38+ | – | Other: PBSC mobilization and leukapheresisA third population characterized by a large density of CD38 and CD34 antigens (CD34+ CD38+). Antigens were expressed as percent positively stained cells as well as intensity of the fluorescence signal quantified as mean fluorescence intensity (MFI) from CD34+ gated cells and from CD45low/SSC total immature cells |
Who may qualify
- Ages
- 25 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome MDS or therapy-related AML) and achieving first CR after induction or salvage therapy. Three populations of CD34+ cells were distinguished based on differential expression of the CD34 and CD38 antigens
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome (MDS) or therapy-related AML)
- Patients achieving first CR after induction or salvage therapy
Key exclusion criteria (3 listed)
- Patients with acute promyelocytic leukemia (APL)
- Concomitant uncontrolled infection, organ dysfunction or medical disease
- left ventricular ejection fraction (LVEF) < 45% as assessed by echocardiography
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 |
|---|---|---|
| PBSC mobilization and leukapheresisMobilization and harvest of autologous PBSCs was scheduled during the recovery phase after the consolidation course. Granulocyte colony stimulating factor (G-CSF) (150 µg/m2/day) was given by daily subcutaneous injection from day 20 of the chemotherapy course until completion of the blood stem cell collections. PBSC collections were performed on 1 - 5 consecutive days during the hematopoietic recovery phase, as soon as the leukocyte count exceeded 2x 109/L. Collections were performed after induction or after consolidation. In cases in which the minimum number of CD34+ cells was not collected, an additional mobilization was performed in steady state. Harvesting was performed using continuous flow blood cell separators. Cells were stored in liquid nitrogen until use, according to standard techniques. | Other | CD34+ CD38+, CD34+ CD38-, CD34+ CD38low |
Primary outcome
Event-free survival (EFS)
Time frame: During the study (1 year)
EFS was defined from date of first apheresis to the date of relapse or death, or last contact with the patient in continuous complete remission
1 secondary outcome
Overall survival (OS)
Time frame: During the study (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 25 Jul 2016.
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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.
Xavier THOMAS, MD-PhD principal investigator
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
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 Acute Myeloid 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 3 inclusion and 3 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 25 Jul 2016. 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?
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?
Event-free survival (EFS) (time frame: During the study (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 25 Jul 2016.