Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

NCT05674539 | Enrolling By Invitation Phase 3 DMC FDA Drug

• 1 other identifier: WHUH-RIC-HSCT-1115
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare outcomes of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients. The main questions it aims to answer are:

• The safety of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years.
• The efficacy of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years. Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Conditions

Acute Myeloid Leukemia, Adult; Myelodysplastic Syndrome(MDS); Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

hematopoietic stem cell transplantation (HSCT); reduced intensity conditioning (RIC); Acute Myeloid Leukemia(AML); Myelodysplastic Syndrome(MDS)

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Survival without relapse or progression of the primary disease. Kaplan-Meier (KM) method was used to estimate median PFS.

  18 months post-randomization

Secondary Outcomes (5)

• Overall Survival (OS)

  18 months post-randomization

• Non-Relapse Mortality (NRM)

  18 months post-randomization

• Disease Relapse

  18 months post-randomization

• Percentage of Participants With Severe Acute Graft-versus-host Disease (GVHD)

  Day 100 post-transplant

• Percentage of Participants With Chronic GVHD

  18 months post-transplant

Other Outcomes (4)

• Percentage of Participants With Neutrophil and Platelet Engraftment

  Days 7 to 60 post-transplant

• Incidence and Percentage of Severe Infection

  18 months post-transplant

• Percentage of Participants With Toxicities

  Days 1 to 60 post-transplant

Study Arms (2)

fludarabine and busulfan

ACTIVE COMPARATOR

fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dase is 150 mg/m\^2) and busulfan (3.2 mg/kg/day, days -3 to days -2, the total dose is 6.4 mg/kg)

Drug: Fludarabine and Busulfan

fludarabine and melphalan

EXPERIMENTAL

fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dose is 150 mg/m\^2) and melphalan (70 mg/m\^2/day, days -3 to days -2, the total dose is 140 mg/m\^2)

Drug: Fludarabine and Melphalan

Interventions

Fludarabine and Busulfan DRUG

Fludarabine with total dose of 150 mg/m\^2 in combination with Busulfan with total dose of 6.4 mg/kg

Also known as: Fludara and Busulfex

fludarabine and busulfan

Fludarabine and Melphalan DRUG

Fludarabine with total dose of 150 mg/m\^2 in combination with Melphalan with total dose of 140 mg/m\^2

Also known as: Busulfex and Fludara

fludarabine and melphalan

Eligibility Criteria

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

You may qualify if:

• Age equal or more than 18 years old.
• Patients diagnosed with AML or MDS.
• Patients who have related or unrelated bone marrow or peripheral blood donors and plan to undergo hematopoietic stem cell transplantation.
• Hct-specific complication index score (HCT-CI) more than or equal to 3 or the age of Patients ≥55 years.
• Sign the informed consent, promise to abide by the research procedures, and cooperate with the implementation of the whole process of the research.

You may not qualify if:

• Patients with central nervous system involvement.
• Patients with HIV seropositive.
• Patients with other serious diseases and a life expectancy of less than six months
• Patients with severe mental or psychological disorders.
• Patients without written informed consent.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

Related Publications (15)

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• Craddock C, Jackson A, Loke J, Siddique S, Hodgkinson A, Mason J, Andrew G, Nagra S, Malladi R, Peniket A, Gilleece M, Salim R, Tholouli E, Potter V, Crawley C, Wheatley K, Protheroe R, Vyas P, Hunter A, Parker A, Wilson K, Pavlu J, Byrne J, Dillon R, Khan N, McCarthy N, Freeman SD. Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia. J Clin Oncol. 2021 Mar 1;39(7):768-778. doi: 10.1200/JCO.20.02308. Epub 2020 Dec 29.

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• Luger SM, Ringden O, Zhang MJ, Perez WS, Bishop MR, Bornhauser M, Bredeson CN, Cairo MS, Copelan EA, Gale RP, Giralt SA, Gulbas Z, Gupta V, Hale GA, Lazarus HM, Lewis VA, Lill MC, McCarthy PL, Weisdorf DJ, Pulsipher MA. Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS. Bone Marrow Transplant. 2012 Feb;47(2):203-11. doi: 10.1038/bmt.2011.69. Epub 2011 Mar 28.

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• Lioure B, Bene MC, Pigneux A, Huynh A, Chevallier P, Fegueux N, Blaise D, Witz B, Delain M, Cornillon J, Luquet I, Blanchet O, Cornillet-Lefebvre P, Carre M, Hunault M, Larosa F, Lamy T, Randriamalala E, Ojeda-Uribe M, Berthou C, Fornecker L, Harousseau JL, Bouscary D, Ifrah N, Cahn JY; GOELAMS. Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study. Blood. 2012 Mar 22;119(12):2943-8. doi: 10.1182/blood-2011-05-352989. Epub 2012 Feb 9.

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• Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schafer-Eckart K, Holler E, Kroger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. doi: 10.1016/S1470-2045(12)70349-2. Epub 2012 Sep 7.

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• Liu H, Zhai X, Song Z, Sun J, Xiao Y, Nie D, Zhang Y, Huang F, Zhou H, Fan Z, Tu S, Li Y, Guo X, Yu G, Liu Q. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol. 2013 Feb 8;6:15. doi: 10.1186/1756-8722-6-15.

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• Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.

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• Shimoni A, Hardan I, Shem-Tov N, Rand A, Herscovici C, Yerushalmi R, Nagler A. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia. 2007 Oct;21(10):2109-16. doi: 10.1038/sj.leu.2404886. Epub 2007 Aug 9.

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• DiMaggio E, Zhou JM, Caddell R, Tombleson R, Perkins J, Anasetti C, Khimani F, Pidala J, Nishihori T, Perez L, Betts B, Fernandez HF, Mishra A. Reduced-intensity fludarabine/melphalan confers similar survival to busulfan/fludarabine myeloablative regimens for patients with acute myeloid leukemia and myelodysplasia. Leuk Lymphoma. 2020 Jul;61(7):1678-1687. doi: 10.1080/10428194.2020.1731498. Epub 2020 Mar 5.

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

fludarabine; Busulfan; fludarabine phosphate; Melphalan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Linghui Xia, Professor

  Department of Hematology, Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Study Record Dates

• First Submitted: December 30, 2022
• First Posted: January 6, 2023
• Study Start: February 15, 2023
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: February 10, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)