Acute Myeloid LeukemiaPhase 3NCT00822393
Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)
A Phase 3 study testing Busulfan and Treosulfan in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by medac GmbH at 33 sites in 6 countries.
Trial summary
This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Busulfan and Treosulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 570 participants
- Where
- 33 sitesin 6 countries
- Study dates
- 24 Nov 2008to 25 Jan 2018
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission at transplant, i.e. blast counts < 5 % in bone marrow) or myelodysplastic syndrome acc. to WHO, 2008 (MDS with blast counts < 20 % in bone marrow during disease history) indicated for allogeneic haematopoietic progenitor cell transplantation but considered to be at increased risk for standard conditioning therapies according to the following criteria:
- patients aged ≥ 50 years at transplant and / or
- patients with a HCT-CI score > 2 [acc. to Sorror et al., 2005]
- Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD). Donor selection is based on molecular high resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci. In case, no class I and class II completely identical donor (10 out of 10 gene loci) can be identified, one antigen disparity (class I) and/or one allele disparity (class II) between patient and donor are acceptable. Conversely, disparity of two antigens (irrespective of the involved gene loci) cannot be accepted. These definitions for the required degree of histocompatibility apply to the selection of related as well as of unrelated donors.
- Adult patients of both gender, age 18 - 70 years
- Karnofsky Index ≥ 60 %
- Written informed consent
- Men capable of reproduction and women of childbearing potential must be willing to consent to using a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter
Who cannot join
- Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1
- Patients considered contra-indicated for allogeneic HSCT due to severe concomitant illness (within three weeks prior to scheduled day -6):
- patients with severe renal impairment like patients on dialysis or prior renal transplantation or S-creatinine > 3.0 x ULN or calculated creatinine-clearance < 60 ml/min
- patients with severe pulmonary impairment, DLCOsb (Hb-adjusted)/or FEV1 < 50 % or severe dyspnoea at rest or requiring oxygen supply
- patients with severe cardiac impairment diagnosed by echocardiography and LVEF < 40 %
- patients with severe hepatic impairment indicated by hyperbilirubinaemia > 3 x ULN or ALT / AST > 5 x ULN
Show all 15Show fewer
- Active malignant involvement of the CNS
- HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
- Previous allogeneic HSCT
- Pleural effusion or ascites > 1.0 L
- Pregnancy or lactation
- Known hypersensitivity to treosulfan, busulfan and/or related ingredients
- Participation in another experimental drug trial within 4 weeks prior to day -6 of the protocol
- Non-cooperative behaviour or non-compliance
- Psychiatric diseases or conditions that might compromise the ability to give informed consent
Trial locations and contacts
33 sites in 6 countries.
33 sites in 6 countries
Germany20 sites
Universitätsklinikum Koeln, Stammzelltransplantation
Cologne, 50937
Universitätsklinikum Carl Gustav Carus Dresden, Med. Klinik I
Dresden, 01307
Klinik für Knochenmarktransplantation
Essen, 45122
Malteser Krankenhaus St. Franziskus-Hospital
Flensburg, 24939
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Universitätsmedizin Goettingen, Haematolgie und Onkologie
Göttingen, 37075
Asklepios Kliniken Hamburg GmbH
Hamburg, 20099
Universitätsklinikum Heidelberg
Heidelberg, 69120
Friedrich-Schiller-Universität Jena
Jena, 07747
Universitätsklinikum Leipzig, Haematologie, internistische Onkologie
Leipzig, 04109
Johannes-Gutenberg-Universität Mainz, III. Medizinische Klinik
Mainz, 55131
Klinikum Rechts der Isar der TU München, III. Med. Klinik
München, 81675
Universitätsklinikum Münster
Münster, 48129
Klinikum Nürnberg, 5. Medizinische Klinik
Nuremberg, 90419
Klinikum Oldenburg gGmbH
Oldenburg, 26133
Klinikum der Universität Regensburg
Regensburg, 93053
Universität Rostock
Rostock, 18057
Universität Tübingen
Tübingen, 72076
Stiftung Deutsche Klinik für Diagnostik
Wiesbaden, 65191
Klinikum der Universität Würzburg
Würzburg, 97070
Italy7 sites
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
Hematology University of Brescia
Brescia, 1-25123
Scientific Institute H. San Raffaele
Milan, 20132
Ospedale Civile Pescara
Pescara, 65123
Policlinico Umberto I Univ. La Sapienza
Rome, 00161
Clinica Ematologica ed Unita di Terapie Cellulari 'Carlo Melzi'
Udine, 33100
Policlinico GB Rossi (Borgo Roma), Div. di Ematologia
Verona, 37134
France2 sites
Centre Hospitalier Lyon Sud
Lyon, 69495
Hopital Saint-Louis
Paris, 75475
Poland2 sites
Medical University of Gdansk
Gdansk, 80-952
Silesian Medical University
Katowice, 40-032
Finland1 site
Helsinki University Central Hospital, Dept. of Medicine
Helsinki, 00290
About this study
Official title: Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard Conditioning Regimens
This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. The protocol is based on results of previous phase I/II trials evaluating Treosulfan/Fludarabine conditioning prior to allogeneic haematopoietic stem cell transplantation. The reference arm (reduced intensity i.v. Busulfan/Fludarabine) is considered to be accepted medical practice for the study patient population.
Read the detailed description
To compare efficacy and safety of Treosulfan-based conditioning (test) with i.v. Busulfan-based reduced intensity conditioning (reference).
The statistical aim of the study is to show non-inferiority with respect to:
Event-free survival (EFS) within 2 years after transplantation. Events are defined as relapse of disease, graft failure or death (whatever occurs first).
- Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
- Comparative evaluation of overall survival (OS) and cumulative incidence of relapse (RI) as well as non-relapse mortality (NRM) and transplantation-related mortality (TRM)within 2 years after transplantation
- Comparative evaluation of day +28 conditional cumulative incidence of engraftment
- Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism
- Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation
- Comparative evaluation of incidence of other CTC grade III/IV adverse events between day -6 and day +28
Individual patients will be followed-up for at most 2 years after transplantation. Three confirmatory interim evaluations and one final analysis are planned, which allow to stop the trial as soon as the question of non-inferiority is answered (as outlined below). In addition, post-surveillance with respect to OS and EFS will be conducted one year after transplantation of the last randomised patient.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Being tested
- Busulfan, Treosulfan
- Keywords
- Treosulfan, Busulfan, Conditioning, Allogeneic, Transplantation
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
4 x 0.8 mg/kg/d Intravenous Day -4 and -3
TreosulfanDrug
10 g/m2/d Intravenous Day -4, -3, -2
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Busulfan Receives: Drug: Busulfan |
| 2 | Experimental | Treosulfan Receives: Drug: Treosulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
Measured: within 2 years after transplantation
Secondary outcomes (1)
Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
Measured: between day -6 and day +28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2009 (estimated)
- Study start24 Nov 2008
- Primary completion25 Jan 2018
- Study completion25 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 570 participants (actual)
Sponsor and investigators
- Lead sponsor
- medac GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dietrich W. Beelen, MD, Principal investigator, University Hospital, Essen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00822393
- Sponsor's protocol ID
- MC-FludT.14/L
- Other IDs
- EudraCT-No.: 2008-002356-18
- Status last verified
- Jul 2020
- First submitted
- 13 Jan 2009
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Remenyi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stolzel F, Schetelig J, Junghanss C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Mico MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socie G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e28-e39. doi: 10.1016/S2352-3026(19)30157-7. Epub 2019 Oct 9.
PubMed 31606445
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard Conditioning Regimens
- ClinicalTrials.gov ID
- NCT00822393
- Acronym / sponsor ID
- MC-FludT.14/L
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Keywords
- Treosulfan, Busulfan, Conditioning, Allogeneic, Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 570 participants (actual)
- Lead sponsor
- medac GmbHIndustry (pharma, biotech, devices)
- Study start
- 24 Nov 2008 (actual)
- Primary completion
- 25 Jan 2018 (actual)
- Study completion
- 25 Jan 2018 (actual)
- First posted
- 14 Jan 2009 (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.
This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. The protocol is based on results of previous phase I/II trials evaluating Treosulfan/Fludarabine conditioning prior to allogeneic haematopoietic stem cell transplantation. The reference arm (reduced intensity i.v. Busulfan/Fludarabine) is considered to be accepted medical practice for the study patient population.
Detailed description
To compare efficacy and safety of Treosulfan-based conditioning (test) with i.v. Busulfan-based reduced intensity conditioning (reference).
The statistical aim of the study is to show non-inferiority with respect to:
Event-free survival (EFS) within 2 years after transplantation. Events are defined as relapse of disease, graft failure or death (whatever occurs first).
- Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
- Comparative evaluation of overall survival (OS) and cumulative incidence of relapse (RI) as well as non-relapse mortality (NRM) and transplantation-related mortality (TRM)within 2 years after transplantation
- Comparative evaluation of day +28 conditional cumulative incidence of engraftment
- Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism
- Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation
- Comparative evaluation of incidence of other CTC grade III/IV adverse events between day -6 and day +28
Individual patients will be followed-up for at most 2 years after transplantation. Three confirmatory interim evaluations and one final analysis are planned, which allow to stop the trial as soon as the question of non-inferiority is answered (as outlined below). In addition, post-surveillance with respect to OS and EFS will be conducted one year after transplantation of the last randomised patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: BusulfanBusulfan |
| 2 | Experimental | Drug: TreosulfanTreosulfan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission at transplant, i.e. blast counts < 5 % in bone marrow) or myelodysplastic syndrome acc. to WHO, 2008 (MDS with blast counts < 20 % in bone marrow during disease history) indicated for allogeneic haematopoietic progenitor cell transplantation but considered to be at increased risk for standard conditioning therapies according to the following criteria:
- Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD). Donor selection is based on molecular high resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci. In case, no class I and class II completely identical donor (10 out of 10 gene loci) can be identified, one antigen disparity (class I) and/or one allele disparity (class II) between patient and donor are acceptable. Conversely, disparity of two antigens (irrespective of the involved gene loci) cannot be accepted. These definitions for the required degree of histocompatibility apply to the selection of related as well as of unrelated donors.
- Adult patients of both gender, age 18 - 70 years
- Karnofsky Index ≥ 60 %
- Written informed consent
Key exclusion criteria (15 listed)
- Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1
- Patients considered contra-indicated for allogeneic HSCT due to severe concomitant illness (within three weeks prior to scheduled day -6):
- Active malignant involvement of the CNS
- HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
- Previous allogeneic HSCT
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 |
|---|---|---|
| Busulfan4 x 0.8 mg/kg/d Intravenous Day -4 and -3 | Drug | 1 |
| Treosulfan10 g/m2/d Intravenous Day -4, -3, -2 | Drug | 2 |
Primary outcome
Event-free survival (EFS)
Time frame: within 2 years after transplantation
1 secondary outcome
Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
Time frame: between day -6 and day +28
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 30 Jul 2020.
- Derived from this study: PubMed 31606445Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Remenyi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stolzel F, Schetelig J, Junghanss C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Mico MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socie G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e28-e39. doi: 10.1016/S2352-3026(19)30157-7. Epub 2019 Oct 9.
- Sponsor's homepageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Dietrich W. Beelen, MD principal investigator
University Hospital, Essen
33 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Busulfan and Treosulfan in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by medac GmbH at 33 sites in 6 countries.
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 8 inclusion and 15 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 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Germany, Italy, France, Poland, Finland and 1 more country. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 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: within 2 years after transplantation). 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 NCT00822393, which also lists 1 linked publication.
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 30 Jul 2020.