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

Primary Purpose

Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
allogeneic stem cell transplantation
5-azacytidine until progress
Sponsored by
Universitätsklinikum Hamburg-Eppendorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring MDS, CMML, allogeneic stem cell transplantation, 5-azacytidine

Eligibility Criteria

55 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Charité Campus Benjamin Franklin
  • Uniklinikum Bonn
  • Universitätsklinikum Dresden
  • Universitätsklinikum Düsseldorf
  • Universitätsklinikum Essen
  • Universitätsklinikum Essen
  • Klinikum der Johann Wolfgang Goethe-Universität
  • Universitätsklinikum Göttingen
  • University Medical Center Hamburg-Eppendorf
  • Medizinische Hochschule Hannover
  • Universität zu Köln
  • Universitätsklinikum Mannheim
  • Klinikum rechts der Isar
  • Universitätsklinikum Münster
  • Klinikum Nürnberg
  • Medizinische Universitätsklinik II
  • Universitätsklinikum Ulm

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

5-azacytidine treatment until progress

allogeneic stem cell transplantation

Arm Description

5-azacytidine until progress

after 4 cycles 5-azacytidine and if donor available: allogeneic stem cell transplantation after reduced intensity conditioning

Outcomes

Primary Outcome Measures

overall survival
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
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
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
overall survival
Comparison of overall survival between both arms (230 pat.). - evaluation of survival status (alive or death/date of death) in the whole study period
impact of Comorbidity-index on outcome
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
compare treatment related mortality in both arms (230 pat.): - death according to treatment in both arms
Evaluation of toxicity
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
quality of life
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

Full Information

First Posted
June 30, 2011
Last Updated
May 26, 2017
Sponsor
Universitätsklinikum Hamburg-Eppendorf
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1. Study Identification

Unique Protocol Identification Number
NCT01404741
Brief Title
5-azacytidine Treatment Versus 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Myelodysplastic Syndrome (MDS)
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2011 (Actual)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia
Keywords
MDS, CMML, allogeneic stem cell transplantation, 5-azacytidine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5-azacytidine treatment until progress
Arm Type
Active Comparator
Arm Description
5-azacytidine until progress
Arm Title
allogeneic stem cell transplantation
Arm Type
Experimental
Arm Description
after 4 cycles 5-azacytidine and if donor available: allogeneic stem cell transplantation after reduced intensity conditioning
Intervention Type
Procedure
Intervention Name(s)
allogeneic stem cell transplantation
Intervention Description
donor available, after 4 cycles 5-azacytidine allogeneic stem cell transplantation after reduced conditioning
Intervention Type
Procedure
Intervention Name(s)
5-azacytidine until progress
Intervention Description
if no donor available 5-azacytidine until progress or toxicities
Primary Outcome Measure Information:
Title
overall survival
Description
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
Time Frame
three years
Secondary Outcome Measure Information:
Title
response
Description
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
Time Frame
three years
Title
event-free survival
Description
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
Time Frame
three years
Title
overall survival
Description
Comparison of overall survival between both arms (230 pat.). - evaluation of survival status (alive or death/date of death) in the whole study period
Time Frame
three years
Title
impact of Comorbidity-index on outcome
Description
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)
Time Frame
three years
Title
Treatment-related mortality
Description
compare treatment related mortality in both arms (230 pat.): - death according to treatment in both arms
Time Frame
three years
Title
Evaluation of toxicity
Description
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
Time Frame
three years
Title
quality of life
Description
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
Time Frame
three years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolaus Kroeger, Prof.
Organizational Affiliation
University Medical Centre Hamburg-Eppendorf, Stem-Cell-Transplantation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité Campus Benjamin Franklin
City
Berlin
Country
Germany
Facility Name
Uniklinikum Bonn
City
Bonn
Country
Germany
Facility Name
Universitätsklinikum Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Klinikum der Johann Wolfgang Goethe-Universität
City
Frankfurt am Main
Country
Germany
Facility Name
Universitätsklinikum Göttingen
City
Göttingen
Country
Germany
Facility Name
University Medical Center Hamburg-Eppendorf
City
Hamburg
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Universität zu Köln
City
Köln
Country
Germany
Facility Name
Universitätsklinikum Mannheim
City
Mannheim
Country
Germany
Facility Name
Klinikum rechts der Isar
City
München
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
Country
Germany
Facility Name
Klinikum Nürnberg
City
Nürnberg
Country
Germany
Facility Name
Medizinische Universitätsklinik II
City
Tübingen
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
Ulm
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34283629
Citation
Kroger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, Stadler M, Kobbe G, Wulf G, Bug G, Schafer-Eckart K, Scheid C, Nolte F, Kronke J, Stelljes M, Beelen D, Heinzelmann M, Haase D, Buchner H, Bleckert G, Giagounidis A, Platzbecker U. Comparison Between 5-Azacytidine Treatment and Allogeneic Stem-Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability (VidazaAllo Study). J Clin Oncol. 2021 Oct 20;39(30):3318-3327. doi: 10.1200/JCO.20.02724. Epub 2021 Jul 20.
Results Reference
derived

Learn more about this trial

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

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