Clinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by medac GmbH
Sponsor:
Information provided by (Responsible Party):
medac GmbH
ClinicalTrials.gov Identifier:
NCT00822393
First received: January 13, 2009
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: Busulfan
Drug: Treosulfan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by medac GmbH:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: within 2 years after transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 960
Study Start Date: November 2008
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Busulfan
Drug: Busulfan
4 x 0.8 mg/kg/d Intravenous Day -4 and -3
Experimental: 2
Treosulfan
Drug: Treosulfan
10 g/m2/d Intravenous Day -4, -3, -2

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).

  1. Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
  2. 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
  3. Comparative evaluation of day +28 conditional cumulative incidence of engraftment
  4. Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism
  5. Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation
  6. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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]
  2. 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.
  3. Adult patients of both gender, age 18 - 70 years
  4. Karnofsky Index ≥ 60 %
  5. Written informed consent
  6. 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

Exclusion Criteria:

  1. Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1
  2. 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
  3. Active malignant involvement of the CNS
  4. HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
  5. Previous allogeneic HSCT
  6. Pleural effusion or ascites > 1.0 L
  7. Pregnancy or lactation
  8. Known hypersensitivity to treosulfan, busulfan and/or related ingredients
  9. Participation in another experimental drug trial within 4 weeks prior to day -6 of the protocol
  10. Non-cooperative behaviour or non-compliance
  11. Psychiatric diseases or conditions that might compromise the ability to give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822393

Contacts
Contact: Joachim Baumgart, PhD +49 4103 8006 ext 437 j.baumgart@medac.de
Contact: Jochen Kehne, PhD + 49 4103 8006 ext 388 j.kehne@medac.de

Locations
Finland
Helsinki University Central Hospital, Dept. of Medicine Active, not recruiting
Helsinki, Finland, 00290
France
Hopital Edouard Herriot Recruiting
Lyon, France, 69437
Contact: Mauricette Michallet, MD    (+33) 4 72-117402    mauricette.michallet@chu-lyon.fr   
Principal Investigator: Mauricette Michallet, MD         
Hopital Saint-Louis Active, not recruiting
Paris, France, 75475
CHU Bordeaux, Hopital Haut-Leveque Active, not recruiting
Pessac, France, 33604
Germany
Klinik für Knochenmarktransplantation Recruiting
Essen, Germany, 45122
Contact: Dietrich W. Beelen, MD    (+49) 201-7 23 ext 3117    dietrich.beelen@uk-essen.de   
Principal Investigator: Dietrich W Beelen, MD         
Universitätsklinikum Freiburg Active, not recruiting
Freiburg, Germany, 79106
Asklepios Kliniken Hamburg GmbH Recruiting
Hamburg, Germany, 20099
Contact: Bertram Glass, M.D.    +49(0)40-18 18-85 ext 3537    b.glass@asklepios.com   
Principal Investigator: Bertram Glass, M.D.         
Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Peter Dreger, MD    (+49) 6221-56 ext 8008    peter.dreger@med.uni-heidelberg.de   
Principal Investigator: Peter Dreger, MD         
Universitätsklinikum Münster Recruiting
Münster, Germany, 48129
Contact: Matthias Stelljes, MD    (+49) 251-835 ext 2801    matthias.stelljes@ukmuenster.de   
Principal Investigator: Matthias Stelljes, MD         
Klinikum Nürnberg, 5. Medizinische Klinik Recruiting
Nürnberg, Germany, 90419
Contact: Kerstin Schaefer-Eckhart, MD    (+49) 911- 3 98 ext 3656    schaefer-eckhart@klinikum-nuernberg.de   
Principal Investigator: Kerstin Schaefer-Eckhart, MD         
Klinikum Oldenburg gGmbH Recruiting
Oldenburg, Germany, 26133
Contact: Jochen Casper, MD    (+49) 441-403 ext 2904    casper.jochen@klinikum-oldenburg.de   
Principal Investigator: Jochen Casper, MD         
Klinikum der Universität Regensburg Recruiting
Regensburg, Germany, 93053
Contact: Ernst Holler, MD    (+49) 941-9 44 ext 5570    ernst.holler@klinik.uni-regensburg.de   
Principal Investigator: Ernst Holler, MD         
Universität Rostock Recruiting
Rostock, Germany, 18057
Contact: Christian Junghanss, MD    (+49) 381-4 94 ext 7424    christian.junghanss@med.uni-rostock.de   
Principal Investigator: Christian Junghanss, MD         
Universität Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Wolfgang Bethge, MD    (+49) 7071-29- ext 8 31 76    wolfgang.bethge@med.uni-tuebingen.de   
Principal Investigator: Wolfgang Bethge, MD         
Klinikum der Universität Würzburg Recruiting
Würzburg, Germany, 97070
Contact: Goetz Ulrich Grigoleit, MD    (+49) 931-2 01-4 ext 0942    grigoleit_g@ukw.de   
Principal Investigator: Goetz Ulrich Grigoleit, MD         
Hungary
St. Istvan and St. Laszlo Hospital of Budapest Recruiting
Budapest, Hungary, 1097
Contact: Tamas Masszi, MD    (+36)1-4 5582 ext 18    tmasszi@laszlokorhaz.hu   
Principal Investigator: Tamas Masszi, MD         
Italy
Ospedale Riuniti Recruiting
Bergamo, Italy, 24128
Contact: Alessandro Rambaldi, MD    (+39) 035-26 ext 68 08    arambaldi@ospedaliriuniti.bergamo.it   
Principal Investigator: Alessandro Rambaldi, MD         
Scientific Institute H. San Raffaele Recruiting
Milan, Italy, 20132
Contact: Fabio Ciceri, MD    (+39) 02-26 43 ext 77 03    ciceri.fabio@hsr.it   
Principal Investigator: Fabio Ciceri, MD         
Policlinico Umberto I Univ. La Sapienza Recruiting
Rome, Italy, 00161
Contact: Anna P Iori, MD    (+39) 06-85795282    iori@bce.uniroma1.it   
Principal Investigator: Anna P Iori, MD         
Clinica Ematologica ed Unita di Terapie Cellulari 'Carlo Melzi' Recruiting
Udine, Italy, 33100
Contact: Francesca Patriarca, MD    (+39) 432 559 ext 662    patriarca.francesca@aoud.sanita.fvg.it   
Principal Investigator: Francesca Patriarca, MD         
Poland
Medical University of Gdansk Recruiting
Gdansk, Poland, 80-952
Contact: Andrzej Hellmann, MD    (+48) 58-349 ext 22 30    klhem@amg.gda.pl   
Principal Investigator: Andrzej Hellmann, MD         
Silesian Medical University Recruiting
Katowice, Poland, 40-032
Contact: Sławomira Kyrcz-Krzemień, MD    (+48) 32 256 ext 28 58    klinhem@sum.edu.pl   
Principal Investigator: Sławomira Kyrcz-Krzemień, MD         
Poznan University of Medical Sciences Not yet recruiting
Poznan, Poland, 60 569
Contact: Mieczyslaw Komarnicki, MD    (+48) 61-8 54 ext 93 83    hematologia@sk1.am.poznan.pl   
Principal Investigator: Mieczyslaw Komarnicki, MD         
Sponsors and Collaborators
medac GmbH
Investigators
Principal Investigator: Dietrich W. Beelen, MD University Hospital, Essen
  More Information

Additional Information:
No publications provided

Responsible Party: medac GmbH
ClinicalTrials.gov Identifier: NCT00822393     History of Changes
Other Study ID Numbers: MC-FludT.14/L, EudraCT-No.: 2008-002356-18
Study First Received: January 13, 2009
Last Updated: May 19, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by medac GmbH:
Treosulfan
Busulfan
Conditioning
Allogeneic
Transplantation

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Busulfan
Treosulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 15, 2014