Leukemia, Myeloid, AcutePhase 2NCT01045382
MSC and HSC Coinfusion in Mismatched Minitransplants
A Phase 2 study testing Mesenchymal stem cells and Isotonic solution in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by University of Liege at 10 sites in Belgium.
Trial summary
The present project aims at evaluating the capacity of MSC to improve one-year overall survival of patients transplanted with HLA-mismatched PBSC from related or unrelated donors after non-myeloablative conditioning. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute, Leukemia, Myelocytic, Chronic
- What is being tested?
- Mesenchymal stem cells and Isotonic solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 10 sitesBelgium
- Study dates
- Jul 2010to Aug 2021
- Phase
- Phase 2
- 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 Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Theoretical indication for a standard allo-transplant, but not feasible because: Age > 55 yrs. Unacceptable end organ performance. Patient's refusal.
- Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
- Male or female; fertile female patients must use a reliable contraception method
- Age ≤ 75 year old
- Informed consent given by patient or his/her guardian if of minor age.
- One or two HLA mismatches with PBSC:
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- One antigenic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
- Two allelic mismatches at HLA-A or -B or -C or -DRB1 or -DQB1
- One antigenic mismatch: 1 allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1.
- One antigenic mismatch at -DQB1 and one other antigenic mismatch at HLA-A or -B or -C or -DRB1
- Patients with one single allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1 can also be included in the protocol.
- Hematological malignancies confirmed histologically and not rapidly progressing:
- AML in complete remission
- ALL in complete remission
- CML unresponsive/intolerant to Imatinib but not in blast crisis
- Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis
- MDS with <5% blasts
- Multiple myeloma not rapidly progressing
- CLL
- Non-Hodgkin's lymphoma (aggressive NHL should be chemosensitive)
- Hodgkin's disease
Who cannot join
- Any condition not fulfilling inclusion criteria
- HIV positive
- Terminal organ failure, except for renal failure (dialysis acceptable)
- Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction <35%; uncontrolled arrhythmia; uncontrolled hypertension
- Pulmonary: DLCO < 35% and/or receiving supplementary continuous oxygen
- Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
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- Uncontrolled infection, arrhythmia or hypertension
- Previous radiation therapy precluding the use of 2 Gy TBI
- 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Belgium10 sites
Hôpital Stuyvenberg
Antwerp, 2060
AZ St-Jan
Bruges, Flanders West, 8000
St-Luc UCL
Brussels, Brabant, 1200
Bordet Institute
Brussels, 1000
Vrije Universiteit Brussel
Brussels, 1050
UZA
Edegem, Antwerpen, 2650
UZ Gent
Ghent, Flanders Ost, 9000
AZ Gasthuisberg Leuven
Leuven, Flamish Brabant, 3000
CHU-ULg
Liège, 4000
Cliniques Universitaires Mont-Godinne
Yvoir, Namur, 5530
About this study
Official title: Co-transplantation of Mesenchymal Stem Cells and HLA-mismatched Allogeneic Hematopoietic Cells After Nonmyeloablative Conditioning: a Phase II Randomized Double-blind Study
The present project aims at evaluating the capacity of MSC to improve one-year overall survival of patients transplanted with HLA-mismatched PBSC from related or unrelated donors after non-myeloablative conditioning.
Co-infusion of MSC has been shown to facilitate engraftment of hematopoietic stem cell (HSC) in an immunodeficient mouse model. In addition, it has been shown that infusion of third party MSC in HSC transplantation could be successfully used as treatment for grade II-IV steroid-refractory acute graft versus host disease.
One hundred and twenty patients with HLA-mismatched donors will be included over 6 years at multiple centers across Belgium through the transplant committee of the Belgian Hematological Society. The conditioning regimen will consist of fludarabine and 2 Gy TBI, followed by the infusion of donor HSC. Patients will be randomized 1/1 in double-blind fashion to receive or not MSC (1.5-.3.0 x106/kg) from third-party (either haploidentical family members or unrelated volunteer) donors on day 0. Postgrafting immunosuppression will combine tacrolimus and MMF. Except for the collection, expansion and infusion of MSC, the clinical management of the patient will not differ from that of routine NM-HCT.
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute, Leukemia, Myelocytic, Chronic, Myeloproliferative Disorders, Myelodysplastic Syndromes, Multiple Myeloma
- Being tested
- Mesenchymal stem cells, Isotonic solution
- Keywords
- HSC transplantation, HLA-mismatched, Mesenchymal stem cells, GVHD, co-infusion
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myeloproliferative Disorders, Myelodysplastic Syndromes, Multiple Myeloma, Leukemia, Lymphocytic, Chronic, B-Cell, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stem cellsBiological
Mesenchymal stem cell injection
Isotonic solutionOther
Isotonic solution injection
| Study group | Role | What they receive |
|---|---|---|
| Mensenchymal Stem Cells | Experimental | Efficacy of MSC infusion on one-year overall survival of patients transplanted with HLA-mismatched PBSC.
Patients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2 Gy total body irradiation.
MSC cells (1,5-3,0 x 10E6 MSC/Kg BW) will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor. Receives: Biological: Mesenchymal stem cells |
| Placebo | Placebo comparator | Patients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2Gy total body irradiation.
Isotonic solution will be injected will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor. Receives: Other: Isotonic solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
One-year overall survival in the 2 arms.
Measured: One year
Secondary outcomes (11)
Incidence of grade II-IV and grade III-IV acute GVDH
Measured: 100 days
Number of absolute donor T cells after HCT in each arm
Measured: 28
Cumulative incidence of non-relapse mortality
Measured: 100, 365 and 730 days
Incidence of extensive chronic GVHD in each arm
Measured: 365 days
Incidence of graft rejection in each arm.
Measured: 365 days
Quality and timing of immunologic reconstitution in each arm.
Measured: 100, 365 and 730 days
Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC
Measured: 40 days
Proportion of patients with measurable disease at HCT who achieve a complete response in each arm.
Measured: 100, 365 and 730 days
Cumulative incidence of relapse
Measured: 365 and 730 days
Incidence of progression-free survival
Measured: 365 and 730 days
Incidence of infections
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2021
- Study completionAug 2021
Why it stopped: recruitment too slow
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Collaborators
- AZ Sint-Jan AV, Ziekenhuis Netwerk Antwerpen (ZNA), Jules Bordet Institute, Universiteit Antwerpen, Universitair Ziekenhuis Brussel, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, University Hospital, Ghent
- Responsible party
- Principal investigator, Yves Beguin, University of Liege
- Investigators
- Yves Beguin, MD, PhD, Principal investigator, CHU-ULgFrédéric Baron, MD, PhD, Study chair, CHU-ULgEvelyne Willems, MD, Principal investigator, CHU-ULgDominik Selleslag, MD, PhD, Principal investigator, AZ BruggePierre Zachée, MD, PhD, Principal investigator, ZNA AntwerpenPhilippe Lewalle, MD, PhD, Principal investigator, Bordet Institute, BrusselsDominique Bron, MD, PhD, Principal investigator, Bordet Institute, BrusselsWilfried Schroyens, MD, PhD, Principal investigator, UZA Antwerpen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01045382
- Sponsor's protocol ID
- TJB0909
- Status last verified
- Aug 2021
- First submitted
- 8 Jan 2010
- Last updated
- 8 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Co-transplantation of Mesenchymal Stem Cells and HLA-mismatched Allogeneic Hematopoietic Cells After Nonmyeloablative Conditioning: a Phase II Randomized Double-blind Study
- ClinicalTrials.gov ID
- NCT01045382
- Acronym / sponsor ID
- TJB0909
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute, Leukemia, Myelocytic, Chronic, Myeloproliferative Disorders, Myelodysplastic Syndromes, Multiple Myeloma
- Keywords
- HSC transplantation, HLA-mismatched, Mesenchymal stem cells, GVHD, co-infusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment too slow
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Collaborators
- AZ Sint-Jan AV, Ziekenhuis Netwerk Antwerpen (ZNA), Jules Bordet Institute, Universiteit Antwerpen, Universitair Ziekenhuis Brussel, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, University Hospital, Ghent
- Study start
- Jul 2010 (actual)
- Primary completion
- Aug 2021 (actual)
- Study completion
- Aug 2021 (actual)
- First posted
- 11 Jan 2010 (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.
The present project aims at evaluating the capacity of MSC to improve one-year overall survival of patients transplanted with HLA-mismatched PBSC from related or unrelated donors after non-myeloablative conditioning.
Co-infusion of MSC has been shown to facilitate engraftment of hematopoietic stem cell (HSC) in an immunodeficient mouse model. In addition, it has been shown that infusion of third party MSC in HSC transplantation could be successfully used as treatment for grade II-IV steroid-refractory acute graft versus host disease.
One hundred and twenty patients with HLA-mismatched donors will be included over 6 years at multiple centers across Belgium through the transplant committee of the Belgian Hematological Society. The conditioning regimen will consist of fludarabine and 2 Gy TBI, followed by the infusion of donor HSC. Patients will be randomized 1/1 in double-blind fashion to receive or not MSC (1.5-.3.0 x106/kg) from third-party (either haploidentical family members or unrelated volunteer) donors on day 0. Postgrafting immunosuppression will combine tacrolimus and MMF. Except for the collection, expansion and infusion of MSC, the clinical management of the patient will not differ from that of routine NM-HCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mensenchymal Stem Cells | Experimental | Biological: Mesenchymal stem cellsEfficacy of MSC infusion on one-year overall survival of patients transplanted with HLA-mismatched PBSC. Patients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2 Gy total body irradiation. MSC cells (1,5-3,0 x 10E6 MSC/Kg BW) will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor. |
| Placebo | Placebo comparator | Other: Isotonic solutionPatients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2Gy total body irradiation. Isotonic solution will be injected will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor. |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- Theoretical indication for a standard allo-transplant, but not feasible because: Age > 55 yrs. Unacceptable end organ performance. Patient's refusal.
- Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
- Male or female; fertile female patients must use a reliable contraception method
- Age ≤ 75 year old
- Informed consent given by patient or his/her guardian if of minor age.
Key exclusion criteria (9 listed)
- Any condition not fulfilling inclusion criteria
- HIV positive
- Terminal organ failure, except for renal failure (dialysis acceptable)
- Uncontrolled infection, arrhythmia or hypertension
- Previous radiation therapy precluding the use of 2 Gy TBI
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 |
|---|---|---|
| Mesenchymal stem cellsMesenchymal stem cell injection | Biological | Mensenchymal Stem Cells |
| Isotonic solutionIsotonic solution injection | Other | Placebo |
Primary outcome
One-year overall survival in the 2 arms.
Time frame: One year
11 secondary outcomes
Incidence of grade II-IV and grade III-IV acute GVDH
Time frame: 100 days
Number of absolute donor T cells after HCT in each arm
Time frame: 28
Cumulative incidence of non-relapse mortality
Time frame: 100, 365 and 730 days
Incidence of extensive chronic GVHD in each arm
Time frame: 365 days
Incidence of graft rejection in each arm.
Time frame: 365 days
Quality and timing of immunologic reconstitution in each arm.
Time frame: 100, 365 and 730 days
Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC
Time frame: 40 days
Proportion of patients with measurable disease at HCT who achieve a complete response in each arm.
Time frame: 100, 365 and 730 days
Cumulative incidence of relapse
Time frame: 365 and 730 days
Incidence of progression-free survival
Time frame: 365 and 730 days
Incidence of infections
Time frame: 100 days
Results and safety
The study was stopped early (reason given: recruitment too slow). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
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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.
Yves Beguin, MD, PhD principal investigator
CHU-ULg
Frédéric Baron, MD, PhD study chair
CHU-ULg
Evelyne Willems, MD principal investigator
CHU-ULg
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal stem cells and Isotonic solution in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by University of Liege at 10 sites in Belgium.
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 21 inclusion and 9 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: stopped early, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Belgium. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: recruitment too slow). Results are not available in the source record.
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?
One-year overall survival in the 2 arms. (time frame: One 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 8 Sep 2021.