Safety and Efficacy of FT14 Conditioning for Allogeneic HSCT in Acute Myeloid Leukemia

NCT07232953 | Active Not Recruiting Phase 2

• 1 other identifier: FT14-Trial
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 13

Brief 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 who are in complete remission.

Conditions

Acute Myeloid Leukaemia (AML); Hematopoietic Stem Cell Transplant (HSCT)

Keywords

AML; Fludarabine; Treosulfan; Allo-HSCT

Outcome Measures

Primary Outcomes (1)

• 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.

  From allo-HSCT to 1-year post allo-HSCT

Secondary Outcomes (14)

• Cumulative incidence of graft failure at day +30

  From allo-HSCT to day +30

• Cumulative incidence of graft failure at day +100

  From allo-HSCT to day +100

• Transplant-related mortality (TRM) at day +100

  From allo-HSCT to day +100

• TRM at 1 year

  From allo-HSCT to 1 year

• TRM at 2 years

  From allo-HSCT to 2 years

Study Arms (1)

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.

Drug: Fludarabine + Treosulfan

Interventions

Fludarabine + Treosulfan DRUG

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

Also known as: Treosulfan, Fludarabine

Fludarabine + Treosulfan conditioning regimen in AML patients

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (13)

Grande Ospedale Metropolitano "Bianco Melacrino Morelli"

Reggio Calabria, Calabria, 89124, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliera Universitaria di Modena

Modena, Emilia-Romagna, 41124, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Friuli Venezia Giulia, 33100, Italy

Location

ASST degli Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

Fondazione IRCCS Ca&#39; Granda Ospedale Maggiore Policlinico,

Milan, Lombardy, 20122, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Azienda Ospedaliera S. Croce e Carle

Cuneo, Piedmont, 12100, Italy

Location

Ospedali Riuniti di Ancona

Ancona, The Marches, 60126, Italy

Location

Ospedale C e G Mazzoni

Ascoli Piceno, The Marches, 63100, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

Ospedale dell'Angelo

Mestre, Veneto, 30174, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Veneto, 37126, Italy

Location

Related Publications (11)

• 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.

  PMID: 29247780 RESULT

• Ruutu 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.

  PMID: 21659356 RESULT

• Casper 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.

  PMID: 22158386 RESULT

• Westerhof 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.

  PMID: 11034090 RESULT

• Fichtner 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.

  PMID: 12651206 RESULT

• Munkelt 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.

  PMID: 18246351 RESULT

• 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.

  PMID: 31606445 RESULT

• Romanski 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.

  PMID: 29557088 RESULT

• Danylesko 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.

  PMID: 21478921 RESULT

• Rambaldi 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.

  PMID: 26429297 RESULT

• Rashidi 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.

  PMID: 29318584 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; treosulfan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Domenico Russo, MD

  ASST Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 18, 2025
• Study Start: November 10, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (13)