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

October 26, 2023 updated by: Universitätsklinikum Hamburg-Eppendorf

Comparison Between 5-azacytidine Treatment and 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability

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. 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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

191

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany
        • Charite Campus Benjamin Franklin
      • Bonn, Germany
        • Uniklinikum Bonn
      • Dresden, Germany, 01307
        • Universitätsklinikum Dresden
      • Düsseldorf, Germany
        • Universitätsklinikum Düsseldorf
      • Essen, Germany
        • Universitätsklinikum Essen
      • Essen, Germany, 45122
        • Universitätsklinikum Essen
      • Frankfurt am Main, Germany
        • Klinikum der Johann Wolfgang Goethe-Universität
      • Göttingen, Germany
        • Universitätsklinikum Göttingen
      • Hamburg, Germany
        • University Medical Center Hamburg-Eppendorf
      • Hannover, Germany
        • Medizinische Hochschule Hannover
      • Köln, Germany
        • Universität zu Köln
      • Mannheim, Germany
        • Universitätsklinikum Mannheim
      • München, Germany
        • Klinikum rechts der Isar
      • Münster, Germany
        • Universitatsklinikum Munster
      • Nürnberg, Germany
        • Klinikum Nürnberg
      • Tübingen, Germany
        • Medizinische Universitätsklinik II
      • Ulm, Germany
        • Universitätsklinikum Ulm

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 5-azacytidine treatment until progress
5-azacytidine 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: three years
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
three years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
response
Time Frame: three years

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
three years
event-free survival
Time Frame: three years

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 period
three years
overall survival
Time Frame: three years

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

- evaluation of survival status (alive or death/date of death) in the whole study period
three years
impact of Comorbidity-index on outcome
Time Frame: three years

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)
three years
Treatment-related mortality
Time Frame: three years

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

- death according to treatment in both arms
three years
Evaluation of toxicity
Time Frame: three years

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

  • 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
three years
quality of life
Time Frame: three years
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
three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Investigators

  • Principal Investigator: Nicolaus Kroeger, Prof., University Medical Centre Hamburg-Eppendorf, Stem-Cell-Transplantation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2011

Primary Completion (Actual)

May 1, 2020

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

June 30, 2011

First Submitted That Met QC Criteria

July 27, 2011

First Posted (Estimated)

July 28, 2011

Study Record Updates

Last Update Posted (Actual)

October 27, 2023

Last Update Submitted That Met QC Criteria

October 26, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VidazaAlloStudy

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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