Acute Myeloid Leukaemia (AML)Phase 2FT14NCT07232953
Safety and Efficacy of FT14 Conditioning for Allogeneic HSCT in Acute Myeloid Leukemia
A Phase 2 study testing Fludarabine + Treosulfan in people with Acute Myeloid Leukaemia (AML) and Hematopoietic Stem Cell Transplant (HSCT), run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 13 sites in Italy.
Trial summary
This is a prospective, multicenter, phase II, open-label, non-randomized clinical trial designed to evaluate the safety and efficacy of the Fludarabine plus Treosulfan 14 g/m² (FT14) conditioning regimen for allogeneic stem cell transplantation (allo-SCT) in patients with Acute Myeloid Leukemia (AML) aged 40-65 years… Read more about this study
- Who is it for?
- Ages 40 to 65 years
- Conditions the study is for
- Acute Myeloid Leukaemia (AML), Hematopoietic Stem Cell Transplant (HSCT)
- What is being tested?
- Fludarabine + Treosulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 13 sitesItaly
- Study dates
- 10 Nov 2022to Jun 2027
- Phase
- Phase 2
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 40 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients >40 <65 years of age
- Diagnosis of AML in first complete remission (CR)/complete remission with incomplete recovery (CRi)/multiflow leukemia free state (MLFS)
- Eligible for allo-SCT from HLA-identical matched related or unrelated donor as defined by molecular high-resolution typing (4 digits) at the following four HLA gene loci (HLA-A, B, C, and DRB1)
- Adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL)
- Adequate renal function (creatinine clearance ≥50 mL/min)
- ECOG Performance Status < 2
- Willing and able to comply with all of the requirements and visits in the protocol.
- Written and signed informed consent
Who cannot join
- AML patients with t(15;17); t(8;21); inv(16)
- Subject has known active CNS involvement with AML.
- Grade >2 NCI-CTCAE (v. 5) adverse events at the time of enrollment
- Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) <40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min.
- The evidence of HBV or HCV active infection (HBV DNA, HCV RNA positive test).
- Patients with HIV infection
Show all 12Show fewer
- Current uncontrolled infections
- Patients with other life-threatening concurrent diseases
- Subjects with known hypersensitivity to any of the component medications
- Participation in another clinical trial within 1 month before the start of this trial
- Participant, both female and male, in childbearing age who do not agree to maintain an active contraceptive practice
- Pregnant or breastfeeding patients during screening
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Italy13 sites
Ospedali Riuniti di Ancona
Ancona, The Marches, 60126
Ospedale C e G Mazzoni
Ascoli Piceno, The Marches, 63100
ASST degli Spedali Civili di Brescia
Brescia, Lombardy, 25123
Azienda Ospedaliera S. Croce e Carle
Cuneo, Piedmont, 12100
Azienda Ospedaliero Universitaria Careggi
Florence, Tuscany, 50134
Ospedale dell'Angelo
Mestre, Veneto, 30174
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico,
Milan, Lombardy, 20122
IRCCS Ospedale San Raffaele
Milan, Lombardy, 20132
Azienda Ospedaliera Universitaria di Modena
Modena, Emilia-Romagna, 41124
Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli
Naples, Campania, 80131
Grande Ospedale Metropolitano "Bianco Melacrino Morelli"
Reggio Calabria, Calabria, 89124
Azienda Sanitaria Universitaria Friuli Centrale
Udine, Friuli Venezia Giulia, 33100
Azienda Ospedaliera Universitaria Integrata Verona
Verona, Veneto, 37126
About this study
Official title: Prospective Phase II Study on Safety and Efficacy of Fludarabine Plus Treosulfan (14g) (FT14) Conditioning Regimen for Allogeneic Stem Cell Transplantation (Allo-SCT) in Acute Myeloid Leukemia (AML) Patients (≥40 <65years) (FT14-Trial)
This is a prospective, multicenter, phase II, open-label, non-randomized clinical trial designed to evaluate the safety and efficacy of the Fludarabine plus Treosulfan 14 g/m² (FT14) conditioning regimen for allogeneic stem cell transplantation (allo-SCT) in patients with Acute Myeloid Leukemia (AML) aged 40-65 years who are in complete remission.
Read the detailed description
This is a prospective, multicenter, phase II, open-label, non-randomized clinical trial designed to evaluate the safety, tolerability, and antileukemic activity of the FT14 conditioning regimen (Fludarabine plus Treosulfan 14 g/m²/day for three consecutive days) in adult patients with Acute Myeloid Leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible patients are 40 to 65 years old, in complete remission (CR), and candidates for allogeneic transplantation according to institutional criteria.
Treosulfan-based conditioning represents an effective alternative to conventional myeloablative regimens, with reduced organ toxicity and favorable immunosuppressive properties. Increasing the treosulfan dose to 14 g/m²/day aims to enhance antileukemic potency while maintaining an acceptable safety profile. Fludarabine provides additional immunosuppression and cytotoxic synergism, facilitating engraftment and disease control.
Enrolled patients will receive the FT14 conditioning regimen followed by allo-HSCT from either a matched related donor (MRD) or a matched unrelated donor (MUD). Haploidentical donors are not included in this study. Graft-versus-host disease (GVHD) prophylaxis, antimicrobial prophylaxis, and supportive care will follow each center's standard procedures.
The primary endpoint is the 1-year leukemia-free survival (LFS). Secondary endpoints include time to engraftment, cumulative incidence of graft failure, transplant-related mortality (TRM) and non-relapse mortality (NRM), relapse incidence, acute and chronic GVHD incidence and severity, overall survival (OS), and graft-versus-host disease-free, relapse-free survival (GRFS). Safety will be assessed through regimen-related toxicities, early and late post-transplant complications, and hematologic recovery kinetics.
The study is designed to provide prospective clinical evidence on the performance, tolerability, and efficacy of the FT14 regimen in adults with AML undergoing allo-HSCT, with the aim of defining its potential role as a conditioning option for this patient population.
- Being tested
- Fludarabine + Treosulfan
- Keywords
- AML, Fludarabine, Treosulfan, Allo-HSCT
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine + TreosulfanDrug
Also called Treosulfan, Fludarabine
Fludarabine (30 mg/m²/d × 5 days) IV infusion days -6 to -2 and Treosulfan (14 g/m²/d × 3 days) IV infusion days -4 to -2
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine + Treosulfan conditioning regimen in AML patients | Experimental | Fludarabine (30 mg/m²/d × 5 days) IV infusion days -6 to -2 and Treosulfan (14 g/m²/d × 3 days) IV infusion days -4 to -2. Receives: Drug: Fludarabine + Treosulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 1-year leukemia -free survival (LFS) after allo-SCT
Proportion of patients alive and free from leukemia at 1 year after allogeneic hematopoietic stem cell transplantation (allo-HSCT), estimated using the Kaplan-Meier method.
Measured: From allo-HSCT to 1-year post allo-HSCT
Secondary outcomes (14)
Cumulative incidence of graft failure at day +30
Cumulative incidence of primary graft failure within 30 days after allo-HSCT, considering death without graft failure as a competing risk.
Measured: From allo-HSCT to day +30
Cumulative incidence of graft failure at day +100
Cumulative incidence of primary or secondary graft failure within 100 days after allo-HSCT, with competing-risk methodology.
Measured: From allo-HSCT to day +100
Transplant-related mortality (TRM) at day +100
Proportion of patients who die without evidence of disease relapse within 100 days after allo-HSCT (non-relapse mortality), estimated using cumulative incidence.
Measured: From allo-HSCT to day +100
TRM at 1 year
Cumulative incidence of TRM within 1 years after allo-HSCT.
Measured: From allo-HSCT to 1 year
TRM at 2 years
Cumulative incidence of TRM within 2 years after allo-HSCT.
Measured: From allo-HSCT to 2 years
Cumulative incidence of acute GVHD at day +100
Proportion of patients developing grade II-IV acute GVHD by day +100, estimated using cumulative incidence with relapse and death as competing events.
Measured: From allo-HSCT to day +100
Cumulative incidence of chronic GVHD at 1 year
Cumulative incidence of chronic GVHD diagnosed within 1 year after allo-HSCT, based on NIH criteria, using competing-risk methodology.
Measured: From allo-HSCT to 1 year
Cumulative incidence of chronic GVHD at 2 years
Cumulative incidence of chronic GVHD diagnosed within 2 years after allo-HSCT, based on NIH criteria.
Measured: From allo-HSCT to 2 years
Relapse incidence at 1 year
Cumulative incidence of leukemia relapse within 1 year after allo-HSCT, analyzed using competing-risk models.
Measured: From allo-HSCT to 1 year
Relapse incidence at 2 year
Cumulative incidence of leukemia relapse within 2 year after allo-HSCT, analyzed using competing-risk models.
Measured: From allo-HSCT to 2 year
Overall survival at 1 year
Proportion of patients alive at 1 year after allo-HSCT, estimated by Kaplan-Meier analysis.
Measured: From allo-HSCT to 1 year
Overall survival at 2 years
Proportion of patients alive at 2 years after allo-HSCT, estimated by Kaplan-Meier method.
Measured: From allo-HSCT to 2 years
Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS) at 1 year
Proportion of patients alive without grade III-IV acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death at 1 year after allo-HSCT.
Measured: From allo-HSCT to 1 year
GRFS at 2 years
Proportion of patients alive without severe acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death within 2 years after allo-HSCT.
Measured: From allo-HSCT to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2025
- Study start10 Nov 2022
- Primary completionJun 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukaemia (AML)Studies 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a multicenter, non-randomized, open-label, single-arm phase II study in which all enrolled patients receive the same conditioning regimen with Fludarabine plus Treosulfan (FT14) before allogeneic stem cell transplantation.
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof Domenico Russo, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Domenico Russo, MD, Principal investigator, Asst Degli Spedali Civili Di Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07232953
- Sponsor's protocol ID
- FT14-Trial
- Acronym
- FT14
- Status last verified
- Nov 2025
- First submitted
- 14 Nov 2025
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: At this time, individual participant data will not be shared outside the study team.
Publications
Shimoni A, Labopin M, Savani B, Hamladji RM, Beelen D, Mufti G, Socie G, Delage J, Blaise D, Chevallier P, Forcade E, Deconinck E, Mohty M, Nagler A. Intravenous Busulfan Compared with Treosulfan-Based Conditioning for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: A Study on Behalf of the Acute Leukemia Working Party of European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018 Apr;24(4):751-757. doi: 10.1016/j.bbmt.2017.12.776. Epub 2017 Dec 13.
PubMed 29247780Ruutu T, Volin L, Beelen DW, Trenschel R, Finke J, Schnitzler M, Holowiecki J, Giebel S, Markiewicz M, Uharek L, Blau IW, Kienast J, Stelljes M, Larsson K, Zander AR, Gramatzki M, Repp R, Einsele H, Stuhler G, Baumgart J, Mylius HA, Pichlmeier U, Freund M, Casper J. Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica. 2011 Sep;96(9):1344-50. doi: 10.3324/haematol.2011.043810. Epub 2011 Jun 9.
PubMed 21659356Casper J, Holowiecki J, Trenschel R, Wandt H, Schaefer-Eckart K, Ruutu T, Volin L, Einsele H, Stuhler G, Uharek L, Blau I, Bornhaeuser M, Zander AR, Larsson K, Markiewicz M, Giebel S, Kruzel T, Mylius HA, Baumgart J, Pichlmeier U, Freund M, Beelen DW. Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning. Bone Marrow Transplant. 2012 Sep;47(9):1171-7. doi: 10.1038/bmt.2011.242. Epub 2011 Dec 12.
PubMed 22158386Westerhof GR, Ploemacher RE, Boudewijn A, Blokland I, Dillingh JH, McGown AT, Hadfield JA, Dawson MJ, Down JD. Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients. Cancer Res. 2000 Oct 1;60(19):5470-8.
PubMed 11034090Fichtner I, Becker M, Baumgart J. Antileukaemic activity of treosulfan in xenografted human acute lymphoblastic leukaemias (ALL). Eur J Cancer. 2003 Apr;39(6):801-7. doi: 10.1016/s0959-8049(02)00767-0.
PubMed 12651206Munkelt D, Koehl U, Kloess S, Zimmermann SY, Kalaaoui RE, Wehner S, Schwabe D, Lehrnbecher T, Schubert R, Kreuter J, Klingebiel T, Esser R. Cytotoxic effects of treosulfan and busulfan against leukemic cells of pediatric patients. Cancer Chemother Pharmacol. 2008 Oct;62(5):821-30. doi: 10.1007/s00280-007-0669-3. Epub 2008 Feb 2.
PubMed 18246351Beelen 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 31606445Romanski M, Wachowiak J, Glowka FK. Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives. Clin Pharmacokinet. 2018 Oct;57(10):1255-1265. doi: 10.1007/s40262-018-0647-4.
PubMed 29557088Danylesko I, Shimoni A, Nagler A. Treosulfan-based conditioning before hematopoietic SCT: more than a BU look-alike. Bone Marrow Transplant. 2012 Jan;47(1):5-14. doi: 10.1038/bmt.2011.88. Epub 2011 Apr 11.
PubMed 21478921Rambaldi A, Grassi A, Masciulli A, Boschini C, Mico MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scime R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-1536. doi: 10.1016/S1470-2045(15)00200-4. Epub 2015 Sep 28.
PubMed 26429297Rashidi A, Weisdorf DJ, Bejanyan N. Treatment of relapsed/refractory acute myeloid leukaemia in adults. Br J Haematol. 2018 Apr;181(1):27-37. doi: 10.1111/bjh.15077. Epub 2018 Jan 9.
PubMed 29318584