5-azacytidine Treatment Versus 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Myelodysplastic Syndrome (MDS)
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- overall survival [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
Secondary Outcome Measures
- response [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
- event-free survival [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
- overall survival [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
- impact of Comorbidity-index on outcome [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)
- Treatment-related mortality [three years]
compare treatment related mortality in both arms (230 pat.): - death according to treatment in both arms
- Evaluation of toxicity [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
- quality of life [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
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Charité Campus Benjamin Franklin | Berlin | Germany | ||
| 2 | Uniklinikum Bonn | Bonn | Germany | ||
| 3 | Universitätsklinikum Dresden | Dresden | Germany | 01307 | |
| 4 | Universitätsklinikum Düsseldorf | Düsseldorf | Germany | ||
| 5 | Universitätsklinikum Essen | Essen | Germany | 45122 | |
| 6 | Universitätsklinikum Essen | Essen | Germany | ||
| 7 | Klinikum der Johann Wolfgang Goethe-Universität | Frankfurt am Main | Germany | ||
| 8 | Universitätsklinikum Göttingen | Göttingen | Germany | ||
| 9 | University Medical Center Hamburg-Eppendorf | Hamburg | Germany | ||
| 10 | Medizinische Hochschule Hannover | Hannover | Germany | ||
| 11 | Universität zu Köln | Köln | Germany | ||
| 12 | Universitätsklinikum Mannheim | Mannheim | Germany | ||
| 13 | Klinikum rechts der Isar | München | Germany | ||
| 14 | Universitätsklinikum Münster | Münster | Germany | ||
| 15 | Klinikum Nürnberg | Nürnberg | Germany | ||
| 16 | Medizinische Universitätsklinik II | Tübingen | Germany | ||
| 17 | Universitätsklinikum Ulm | Ulm | Germany |
Sponsors and Collaborators
- Universitätsklinikum Hamburg-Eppendorf
Investigators
- Principal Investigator: Nicolaus Kroeger, Prof., University Medical Centre Hamburg-Eppendorf, Stem-Cell-Transplantation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VidazaAlloStudy