5-azacytidine Treatment Versus 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Myelodysplastic Syndrome (MDS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by Universitätsklinikum Hamburg-Eppendorf
Sponsor:
Information provided by:
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01404741
First received: June 30, 2011
Last updated: July 27, 2011
Last verified: July 2011
  Purpose

5-azacytidine treatment prolongs survival in patients with myelodysplastic syndrome (MDS), but does not cure the disease. Allogeneic stem cell transplantation is a curative treatment option but is associated with a high risk treatment-related morbidity and mortality. Dose-reduced conditioning prior transplantation allows also treatment of elderly patients with MDS. In the current trial allogeneic stem cell transplantation will be compared to 5-azacytidine only treatment according to donor availability in elderly patients with MDS (55-70 years).


Condition Intervention Phase
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Procedure: allogeneic stem cell transplantation
Procedure: 5-azacytidine until progress
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison Between 5-azacytidine Treatment and 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]
    compare to overall survival of patients who receive after 4 cycles of 5-azacytidine either allogeneic stem cell transplantation or continuous 5-azacytidine if no compatible donor is available overall 230 patients


Secondary Outcome Measures:
  • response [ Time Frame: three years ] [ Designated as safety issue: No ]

    Comparison of response according to International Working Group Response Criteria between both arms:

    - Examinations of bone marrow (count of blasts) and peripheral blood (hematological improvement)after schedule of study assessments (after cycle 4 in both arms, after cycle 8 and after months 12-24-36 in the 5-azacytidine treatment and on day 100, day 180, months 12-24-36 after allogeneic stem cell transplantation


  • event-free survival [ Time Frame: three years ] [ Designated as safety issue: No ]

    comparison of event free survival in both arms (230 pat.):

    - evaluation of survival status (relapse, date of relapse, alive or death) in the whole study periode


  • overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]

    Comparison of overall survival between both arms (230 pat.).

    - evaluation of survival status (alive or death/date of death) in the whole study periode


  • impact of Comorbidity-index on outcome [ Time Frame: three years ] [ Designated as safety issue: No ]

    impact of comorbidity-index on outcome after study entry and prior to allogeneic stem cell transplantation (according definitions and weighted scores of comorbidities by Sorror et al):

    • physical examination
    • laboratory values(creatinine,Alt, AST, bilirubin, etc.)
    • apparative diagnostics (echo,lufu,ECG)

  • Treatment-related mortality [ Time Frame: three years ] [ Designated as safety issue: No ]

    compare treatment related mortality in both arms (230 pat.):

    - death according to treatment in both arms


  • Evaluation of toxicity [ Time Frame: three years ] [ Designated as safety issue: Yes ]

    the evaluation of toxicity will be performed according to the reporting guidelines as per NCI CTCAE in the whole study periode:

    • adverse events grade 3 and 4
    • cytopenia grade 3 and 4 only be reported as AE which are judged by the investigator as clinically relevant

  • quality of life [ Time Frame: three years ] [ Designated as safety issue: No ]
    Comparison of quality of life between both arms with the quality of life core questionnaire QLQ-C30 and the treatment specific high-dose chemotherapy module QLQ HD-C29 to assess the quality of life of cancer patient. The questionnaire has to be answered after the fourth cycle, 6 months, 1 year, 2 years and 3 years after both treatment arms


Estimated Enrollment: 230
Study Start Date: June 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 5-azacytidine treatment until progress Procedure: 5-azacytidine until progress
if no donor available 5-azacytidine until progress or toxicities
Experimental: allogeneic stem cell transplantation
after 4 cycles 5-azacytidine and if donor available: allogeneic stem cell transplantation after reduced intensity conditioning
Procedure: allogeneic stem cell transplantation
donor available, after 4 cycles 5-azacytidine allogeneic stem cell transplantation after reduced conditioning

  Eligibility

Ages Eligible for Study:   55 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with proven de novo or therapy-related MDS / CMML (WBC <13 GPT/l)according to FAB and risk profile according to IPSS: intermediate II- risk or high-risk or intermediate I with high-risk cytogenetic (according to IPSS, taking into account that IPSS, however, was not validated for t- MDS), patients with secondary AML (according to WHO) and blasts ≤ 30 % (= RAEB-t according to FAB)
  • Previously untreated or maximal 1 cycle of 5-azacytidine (Vidaza®)
  • Male or Female; Age 55 - 70 years
  • Understand and voluntarily sign an informed consent form
  • ECOG performance status of ≤ 2 at study entry
  • Adequate renal and liver function: creatinine and bilirubin < 3 x the upper limit of normal
  • Sufficient cardiac function (ejection fraction > 30 %)

Exclusion Criteria:

  • Blasts > 30 % in bone marrow at time of diagnosis
  • Central nervous involvement
  • Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as
  • Total bilirubin, SGPT or SGOT ≥ 3 times upper the normal level
  • Left ventricular ejection fraction < 30 %
  • Creatinine clearance < 30 ml/min
  • DLCO < 35 % and/or receiving supplementary continuous oxygen
  • Pregnant or breastfeeding female subject
  • Patients with a life-expectancy of less than six months because of another debilitating disease
  • Serious psychiatric or psychological disorders
  • Uncontrolled invasive fungal infection at time of registration
  • Known positive for HIV or acute infectious hepatitis, type A, B or C
  • Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment until the end of the study
  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: NCT01404741

Contacts
Contact: Nicolaus Kroeger, Prof. +49-40-7410-55864 nkroeger@uke.uni-hamburg.de
Contact: Marion Heinzelmann +49-40-7410-54188 mheinzel@uke.uni-hamburg.de

Locations
Germany
Charité Campus Benjamin Franklin Not yet recruiting
Berlin, Germany
Contact: Lutz Uharek, Prof. Dr.         
Principal Investigator: Lutz Uharek, Prof. Dr.         
Uniklinikum Bonn Not yet recruiting
Bonn, Germany
Contact: Marie v. Lilienfeld-Toal, PD Dr.         
Principal Investigator: Marie v.Lilienfeld-Toal, PD Dr.         
Universitätsklinikum Dresden Recruiting
Dresden, Germany, 01307
Contact: Uwe Platzbecker, PD Dr.         
Principal Investigator: Uwe Platzbecker, PD Dr.         
Universitätsklinikum Düsseldorf Not yet recruiting
Düsseldorf, Germany
Contact: Guido Kobbe, PD Dr.         
Principal Investigator: Guido Kobbe, PD Dr.         
Universitätsklinikum Essen Not yet recruiting
Essen, Germany, 45122
Contact: Dietrich W. Beelen, Prof. Dr.         
Principal Investigator: Dietrich W. Beelen, Prof. Dr.         
Universitätsklinikum Essen Not yet recruiting
Essen, Germany
Contact: Richard Noppeney, Dr.         
Principal Investigator: Richard Noppeney, Dr.         
Klinikum der Johann Wolfgang Goethe-Universität Not yet recruiting
Frankfurt am Main, Germany
Contact: Gesine Bug, Dr.         
Principal Investigator: Gesine Bug, Dr.         
Universitätsklinikum Göttingen Not yet recruiting
Göttingen, Germany
Contact: Gerald Wulf, Prof. Dr.         
Principal Investigator: Gerald Wulf, Prof. Dr.         
University Medical Center Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: Nicolaus Kroeger, Prof.    +49-40-7410-55864    nkroeger@uke.uni-hamburg.de   
Contact: Marion Heinzelmann    +49-40-7410-54188    mheinzel@uke.uni-hamburg.de   
Principal Investigator: Nicolaus Kroeger, Prof.         
Medizinische Hochschule Hannover Not yet recruiting
Hannover, Germany
Contact: Michael Stadler, Dr.Dr.         
Principal Investigator: Michael Stadler, Dr.Dr.         
Universität zu Köln Not yet recruiting
Köln, Germany
Contact: Christof Scheid, PD Dr.         
Principal Investigator: Christof Scheid, PD Dr.         
Universitätsklinikum Mannheim Not yet recruiting
Mannheim, Germany
Contact: Stefan A. Klein, PD Dr.         
Principal Investigator: Stefan A. Klein, PD Dr.         
Klinikum rechts der Isar Not yet recruiting
München, Germany
Contact: Helge Menzel, Dr         
Principal Investigator: Helge Menzel, Dr.         
Universitätsklinikum Münster Not yet recruiting
Münster, Germany
Contact: Matthias Stelljes, PD Dr.         
Principal Investigator: Matthias Stelljes, PD Dr.         
Klinikum Nürnberg Not yet recruiting
Nürnberg, Germany
Contact: Kerstin Schäfer-Eckart, Dr.         
Principal Investigator: Kerstin Schäfer-Eckart, Dr.         
Medizinische Universitätsklinik II Not yet recruiting
Tübingen, Germany
Contact: Wolfgang Bethge, PD Dr.         
Principal Investigator: Wolfgang Betghe, PD Dr.         
Universitätsklinikum Ulm Not yet recruiting
Ulm, Germany
Contact: Richard F. Schlenk, PD Dr.         
Principal Investigator: Richard F. Schlenk, PD Dr.         
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Principal Investigator: Nicolaus Kroeger, Prof. University Medical Centre Hamburg-Eppendorf, Stem-Cell-Transplantation
  More Information

No publications provided

Responsible Party: Prof. N. Kroeger, University Medical Center Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01404741     History of Changes
Other Study ID Numbers: VidazaAlloStudy
Study First Received: June 30, 2011
Last Updated: July 27, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
MDS
CMML
allogeneic stem cell transplantation
5-azacytidine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014