NCT00822393

Brief 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. 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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
570

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Nov 2008

Longer than P75 for phase_3

Geographic Reach
6 countries

33 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 24, 2008

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 13, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2009

Completed
9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 25, 2018

Completed
Last Updated

July 30, 2020

Status Verified

July 1, 2020

Enrollment Period

9.2 years

First QC Date

January 13, 2009

Last Update Submit

July 29, 2020

Conditions

Acute Myeloid LeukemiaMyelodysplastic Syndrome

Keywords

TreosulfanBusulfanConditioningAllogeneicTransplantation

Outcome Measures

Primary Outcomes (1)

  • Event-free survival (EFS)

    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

    between day -6 and day +28

Study Arms (2)

1

ACTIVE COMPARATOR

Busulfan

Drug: Busulfan

2

EXPERIMENTAL

Treosulfan

Drug: Treosulfan

Interventions

BusulfanDRUG

4 x 0.8 mg/kg/d Intravenous Day -4 and -3

1
TreosulfanDRUG

10 g/m2/d Intravenous Day -4, -3, -2

2

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

Helsinki University Central Hospital, Dept. of Medicine

Helsinki, 00290, Finland

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

Universitätsklinikum Koeln, Stammzelltransplantation

Cologne, 50937, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden, Med. Klinik I

Dresden, 01307, Germany

Location

Klinik für Knochenmarktransplantation

Essen, 45122, Germany

Location

Malteser Krankenhaus St. Franziskus-Hospital

Flensburg, 24939, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsmedizin Goettingen, Haematolgie und Onkologie

Göttingen, 37075, Germany

Location

Asklepios Kliniken Hamburg GmbH

Hamburg, 20099, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Friedrich-Schiller-Universität Jena

Jena, 07747, Germany

Location

Universitätsklinikum Leipzig, Haematologie, internistische Onkologie

Leipzig, 04109, Germany

Location

Johannes-Gutenberg-Universität Mainz, III. Medizinische Klinik

Mainz, 55131, Germany

Location

Klinikum Rechts der Isar der TU München, III. Med. Klinik

München, 81675, Germany

Location

Universitätsklinikum Münster

Münster, 48129, Germany

Location

Klinikum Nürnberg, 5. Medizinische Klinik

Nuremberg, 90419, Germany

Location

Klinikum Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Klinikum der Universität Regensburg

Regensburg, 93053, Germany

Location

Universität Rostock

Rostock, 18057, Germany

Location

Universität Tübingen

Tübingen, 72076, Germany

Location

Stiftung Deutsche Klinik für Diagnostik

Wiesbaden, 65191, Germany

Location

Klinikum der Universität Würzburg

Würzburg, 97070, Germany

Location

St. Istvan and St. Laszlo Hospital of Budapest

Budapest, 1097, Hungary

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Hematology University of Brescia

Brescia, 1-25123, Italy

Location

Scientific Institute H. San Raffaele

Milan, 20132, Italy

Location

Ospedale Civile Pescara

Pescara, 65123, Italy

Location

Policlinico Umberto I Univ. La Sapienza

Rome, 00161, Italy

Location

Clinica Ematologica ed Unita di Terapie Cellulari 'Carlo Melzi'

Udine, 33100, Italy

Location

Policlinico GB Rossi (Borgo Roma), Div. di Ematologia

Verona, 37134, Italy

Location

Medical University of Gdansk

Gdansk, 80-952, Poland

Location

Silesian Medical University

Katowice, 40-032, Poland

Location

Related Publications (1)

  • 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: 31606445DERIVED

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyelodysplastic Syndromes

Interventions

Busulfantreosulfan

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Diseases

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur Compounds

Study Officials

  • Dietrich W. Beelen, MD

    University Hospital, Essen

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

January 13, 2009

First Posted

January 14, 2009

Study Start

November 24, 2008

Primary Completion

January 25, 2018

Study Completion

January 25, 2018

Last Updated

July 30, 2020

Record last verified: 2020-07

Locations

FI(1)IT(7)FR(2)PL(2)HU(1)DE(20)