Acute Myeloid Leukemia in RemissionPhase 2HLANCT03852407
Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning
A Phase 2 study testing Thymoglobulin, Melphalan and Fludarabine in people with Acute Myeloid Leukemia in Remission and Myelodysplastic Syndromes, run by University of Liege at 10 sites in Belgium.
Trial summary
The present project aims at comparing two conditioning regimens (FM-PTCy vs FM-ATG). The hypothesis is that one or the two regimens will lead to a 2-year cGRFS rate improvement from 30% (the cGRFS rate with FM without ATG/PTCy) to 45% (Pick-a-winner phase 2 randomized study). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia in Remission, Myelodysplastic Syndromes, Chronic Myeloid Leukemia in Remission
- What is being tested?
- Thymoglobulin, Melphalan and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 10 sitesBelgium
- Study dates
- 4 Feb 2019to 1 Nov 2038
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients V.1.1. Diseases
- Hematological malignancies confirmed histologically:
- AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count < 10 000 x109/mL);
- MDS;
- CML in CP or AP;
- MPD not in blast crisis,
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- MDS/MPD overlap,
- ALL in CR;
- Multiple myeloma;
- CLL;
- Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
- Hodgkin's disease with chemosensitive disease or responding to checkpoint inhibitors.
- Clinical situations
- Theoretical indication for a standard allo-transplant, but not feasible because:
- Age > 50 yrs;
- Unacceptable end organ performance;
- The physician's decision;
- The patient's decision
- Underlying 'lower risk' disease, for which Reduced Intensity Conditioning is preferred (eg CLL, MCL)
- Other inclusion criteria
- Male or female; fertile patients must use a reliable contraception method;
- Age 18-75 yrs (children of any age are not allowed in the protocol);
- Informed consent given by patient or his/her guardian if indicated.
- Donors
- Male or female;
- Any age;
- Human Leukocyte Antigen (HLA)-identical sibling donor or 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched unrelated donor;
- Weight > 15 Kg (because of leukapheresis);
- Fulfills criteria for allogeneic Peripheral Blood Stem Cell (PBSC) donation according to standard procedures;
- Informed consent given by donor or his/her guardian if indicated, as per donor center standard procedures.
Who cannot join
- Patients
- Any condition not fulfilling inclusion criteria;
- Human Immunodeficiency Virus positive;
- Non-hematological malignancy(ies) (except non-melanoma skin cancer) active < 3 years before Hematopoietic Cell Transplantation (HCT).
- Life expectancy severely limited by disease other than malignancy;
- Central Nervous System involvement with disease refractory to intrathecal chemotherapy.
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- Terminal organ failure, except for renal failure (dialysis acceptable)
- Cardiac: Symptomatic coronary artery disease; ejection fraction <40%; uncontrolled arrhythmia, uncontrolled hypertension;
- Pulmonary: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)< 40% and/or receiving supplementary continuous oxygen, Forced Expiratory Volume in 1 Second (FEV1)< 40%;
- 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;
- Uncontrolled infection;
- Karnofsky Performance Score <70%;
- Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
- Patient is a female who is pregnant or breastfeeding;
- Any condition precluding the use of melphalan or Thymoglobulin;
- Donors
- Any condition not fulfilling inclusion criteria;
- Unable to undergo leukapheresis because of poor vein access or other reasons.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Belgium10 sites, 10 recruiting
- Recruiting
ZNA Stuivenberg
Antwerp, 2060
Dimitri Breems, MD PhD, dimitri.Breems@zna.be
- Recruiting
AZ Sint Jan Brugge
Bruges, 8000
Dominik Selleslag, MD, PhD, dominik.selleslag@AZsintjan.be
- Recruiting
IJ Bordet
Brussels, 1000
Philippe Lewalle, MD PhD, philippe.lewalle@bordet.be
- Recruiting
UZ Brussel
Brussels, 1090
Ann De Becker, MD PhD, ann.debecker@uzbrussel.be
Rik Schots, MD PhD
- Recruiting
UCL St Luc
Brussels, 1200
Xavier Poiré, MD, xavier.poire@uclouvain.be
- Recruiting
UZ Gent
Ghent, 9000
Tessa Kerre, MD PhD, t.Kerre@UGent.be
- Recruiting
UZ Leuven
Leuven, 3000
Johan Maertens, MD PhD, johan.maertens@uzleuven.be
Hélène Schoemans, MD PhD
- Recruiting
CHU de Liège
Liège, 4000
Frédéric Baron, MD, PhD, +3243667201 ext. +3243667201, F.Baron@uliege.be
Yves Beguin, MD, PhD, +3243667201 ext. +3243667201, yves.beguin@chuliege.be
- Recruiting
AZ Delta Roeselare
Roeselare, 8800
Dries Deeren, MD, dries.deeren@AZdelta.be
- Recruiting
CHU UCL Namur Godinne
Yvoir, 5530
Carlos Graux, MD PhD, carlos.graux@uclouvain.be
About this study
Official title: Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning: a Phase II Randomized Study From the Belgian Hematology Society (BHS)
The present project aims at comparing two conditioning regimens (FM-PTCy vs FM-ATG). The hypothesis is that one or the two regimens will lead to a 2-year cGRFS rate improvement from 30% (the cGRFS rate with FM without ATG/PTCy) to 45% (Pick-a-winner phase 2 randomized study).
Read the detailed description
This study is a multicenter, randomized, open-label, phase II study pick-a-winner study, comparing 2 conditioning regimens. A total of 114 eligible patients with HLA-matched donors will be randomized 1:1 between the FM-PTCy arm and the FM-ATG arm, with stratification for donor type (related or unrelated). The recruitment period is 3 years with a 5-year follow-up plus a 10-year additional long-term follow-up (for GVHD status, disease status, second malignancy and QOL). The whole study will be completed within 18 years.
- Conditions
- Acute Myeloid Leukemia in Remission, Myelodysplastic Syndromes, Chronic Myeloid Leukemia in Remission, Myeloproliferative Syndrome, Myeloproliferative Disorder, Acute Lymphoid Leukemia in Remission
- Being tested
- Thymoglobulin, Melphalan, Fludarabine, Cyclophosphamid
- Keywords
- hematological malignancies, Graft versus host disease, GVHD, Progression free survival, Allogeneic hematopoeitic cell transplantation, HLA-matched donor, reduced intensity conditioning, Overall survival, ATG PK, Immunosuppressive regimen, Prophylaxis
- Medical subject headings
- Myelodysplastic Syndromes, Myeloproliferative Disorders, Multiple Myeloma, Leukemia, B-Cell, Lymphoma, Non-Hodgkin, Hodgkin Disease, Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinDrug
Also called ATG
ATG: 2.5 mg /kg/day on day -2 and -1 (day 0 is allogenic transplantation)
MelphalanDrug
Also called alkeran
100mg/m² on day -2
FludarabineDrug
30mg/m² on days -6, -5, -4, -3, and -2
CyclophosphamidDrug
Also called PTCy
50 mg/kg on days +3 and +4.
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine-Melphalan-Cyclophosphamide | Experimental | FM-PTCy conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and cyclophosphamide 50 mg/kg on days +3 and +4. Receives: Drug: Melphalan; Drug: Fludarabine; Drug: Cyclophosphamid |
| Fludarabine-Melphalan-thymoglobulin | Experimental | FM-ATG conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and ATG (Thymoglobulin®, Genzyme), at a dose of 2.5 mg/kg/d on days -2 and -1. Receives: Drug: Thymoglobulin; Drug: Melphalan; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Current GVHD-free, relapse-free survival (cGRFS)
To assess the current GVHD-free, relapse-free survival (cGRFS) for patients in the 2 arms
Measured: 15 years (the primary endpoint will be first assessed after 191 events have been reached)
Secondary outcomes (8)
cGRFS according donor
To assess cGRFS for patients conditioned with FM-PTCy or FM-ATG separately in those transplanted with a related or an unrelated donor
Measured: 15 years
Relapse/progression rate
To assess the relapse/progression rate for patients conditioned with FM-PTCy or FM-ATG
Measured: 15 years
Rate aGVHD
To assess rate of grade II-IV and III-IV acute GVHD (Graft-versus-host disease) in patients conditioned with FM or FM-ATG.
Measured: 6 months
Rate cGVHD
To assess rate of grade of moderate-severe chronic GVHD in patients conditioned with FM or FM-ATG.
Measured: 24 months
Rate of Nonrelapse Mortality (NRM)
To assess rate of Nonrelapse Mortality in patients conditioned with FM-PTCy or FM-ATG.
Measured: 15 years
Rate of Leukemia Free Survival (LFS)
To assess rate of Leukemia Free Survival in patients conditioned with FM-PTCy or FM-ATG.
Measured: 15 years
Rate of Overall Survival (OS)
To assess rate of Overall Survival in patients conditioned with FM-PTCy or FM-ATG.
Measured: 15 years
Proportion of patients alive
To assess the proportion of patients alive without active disease and without systemic immunosuppression
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2019
- Study start4 Feb 2019
- Primary completion1 Nov 2033 (estimated)
- Study completion1 Nov 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia in RemissionStudies 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
- None (open label)
- Enrolment
- 114 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Collaborators
- Belgian Hematological Society
- Responsible party
- Principal investigator, Frédéric Baron, University of Liege
- Investigators
- Frédéric Baron, MD,Ph, Principal investigator, Centre Hospitalier Universitaire de Liege
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03852407
- Sponsor's protocol ID
- BHS-TC14
- Other IDs
- 2017-000824-91, 2017
- Acronym
- HLA
- Status last verified
- Oct 2022
- First submitted
- 21 Jan 2019
- Last updated
- 12 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning: a Phase II Randomized Study From the Belgian Hematology Society (BHS)
- ClinicalTrials.gov ID
- NCT03852407
- Acronym / sponsor ID
- HLA / BHS-TC14
- Conditions
- Acute Myeloid Leukemia in Remission, Myelodysplastic Syndromes, Chronic Myeloid Leukemia in Remission, Myeloproliferative Syndrome, Myeloproliferative Disorder, Acute Lymphoid Leukemia in Remission
- Keywords
- hematological malignancies, Graft versus host disease, GVHD, Progression free survival, Allogeneic hematopoeitic cell transplantation, HLA-matched donor, reduced intensity conditioning, Overall survival
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 114 participants (estimated)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Collaborators
- Belgian Hematological Society
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 1 Nov 2033 (estimated)
- Study completion
- 1 Nov 2038 (estimated)
- First posted
- 25 Feb 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.
The present project aims at comparing two conditioning regimens (FM-PTCy vs FM-ATG). The hypothesis is that one or the two regimens will lead to a 2-year cGRFS rate improvement from 30% (the cGRFS rate with FM without ATG/PTCy) to 45% (Pick-a-winner phase 2 randomized study).
Detailed description
This study is a multicenter, randomized, open-label, phase II study pick-a-winner study, comparing 2 conditioning regimens. A total of 114 eligible patients with HLA-matched donors will be randomized 1:1 between the FM-PTCy arm and the FM-ATG arm, with stratification for donor type (related or unrelated). The recruitment period is 3 years with a 5-year follow-up plus a 10-year additional long-term follow-up (for GVHD status, disease status, second malignancy and QOL). The whole study will be completed within 18 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fludarabine-Melphalan-Cyclophosphamide | Experimental | Drug: Melphalan, Drug: Fludarabine, Drug: CyclophosphamidFM-PTCy conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and cyclophosphamide 50 mg/kg on days +3 and +4. |
| Fludarabine-Melphalan-thymoglobulin | Experimental | Drug: Thymoglobulin, Drug: Melphalan, Drug: FludarabineFM-ATG conditioning will consist in IV fludarabine 30 mg/m2 on days -6, -5, -4, -3, and -2 (total dose 150 mg/m2), melphalan given at the dose of 100 mg/m2 on day -2, and ATG (Thymoglobulin®, Genzyme), at a dose of 2.5 mg/kg/d on days -2 and -1. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Patients V.1.1. Diseases
- AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count < 10 000 x109/mL);
- MDS;
- CML in CP or AP;
- MPD not in blast crisis,
Key exclusion criteria (18 listed)
- Patients
- Any condition not fulfilling inclusion criteria;
- Human Immunodeficiency Virus positive;
- Non-hematological malignancy(ies) (except non-melanoma skin cancer) active < 3 years before Hematopoietic Cell Transplantation (HCT).
- Life expectancy severely limited by disease other than malignancy;
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 |
|---|---|---|
| ThymoglobulinAlso: ATGATG: 2.5 mg /kg/day on day -2 and -1 (day 0 is allogenic transplantation) | Drug | Fludarabine-Melphalan-thymoglobulin |
| MelphalanAlso: alkeran100mg/m² on day -2 | Drug | Fludarabine-Melphalan-Cyclophosphamide, Fludarabine-Melphalan-thymoglobulin |
| Fludarabine30mg/m² on days -6, -5, -4, -3, and -2 | Drug | Fludarabine-Melphalan-Cyclophosphamide, Fludarabine-Melphalan-thymoglobulin |
| CyclophosphamidAlso: PTCy50 mg/kg on days +3 and +4. | Drug | Fludarabine-Melphalan-Cyclophosphamide |
Primary outcome
Current GVHD-free, relapse-free survival (cGRFS)
Time frame: 15 years (the primary endpoint will be first assessed after 191 events have been reached)
To assess the current GVHD-free, relapse-free survival (cGRFS) for patients in the 2 arms
8 secondary outcomes
cGRFS according donor
Time frame: 15 years
Relapse/progression rate
Time frame: 15 years
Rate aGVHD
Time frame: 6 months
Rate cGVHD
Time frame: 24 months
Rate of Nonrelapse Mortality (NRM)
Time frame: 15 years
Rate of Leukemia Free Survival (LFS)
Time frame: 15 years
Rate of Overall Survival (OS)
Time frame: 15 years
Proportion of patients alive
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
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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.
Frédéric Baron, MD,Ph principal investigator
Centre Hospitalier Universitaire de Liege
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 Thymoglobulin, Melphalan and Fludarabine in people with Acute Myeloid Leukemia in Remission and Myelodysplastic Syndromes, 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 30 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 12 Oct 2022. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Frédéric Baron, MD,Ph (+32 4 366 72 01 ext. 0032497121806, F.Baron@uliege.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Current GVHD-free, relapse-free survival (cGRFS) (time frame: 15 years (the primary endpoint will be first assessed after 191 events have been reached)). 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 12 Oct 2022.