5-azacytidine Treatment Versus 5-azacytidine Followed by Allogeneic Stem Cell Transplantation in Elderly Patients With Myelodysplastic Syndrome (MDS)
- Conditions
- Myelodysplastic SyndromeChronic Myelomonocytic Leukemia
- Interventions
- Procedure: allogeneic stem cell transplantationProcedure: 5-azacytidine until progress
- Registration Number
- NCT01404741
- Lead Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 191
- 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 %)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description allogeneic stem cell transplantation allogeneic stem cell transplantation after 4 cycles 5-azacytidine and if donor available: allogeneic stem cell transplantation after reduced intensity conditioning 5-azacytidine treatment until progress 5-azacytidine until progress 5-azacytidine until progress
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 periodoverall 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 periodresponse 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 transplantationimpact 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 armsEvaluation 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 relevantquality 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
Trial Locations
- Locations (16)
Charité Campus Benjamin Franklin
🇩🇪Berlin, Germany
Uniklinikum Bonn
🇩🇪Bonn, Germany
Universitätsklinikum Dresden
🇩🇪Dresden, Germany
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Klinikum der Johann Wolfgang Goethe-Universität
🇩🇪Frankfurt am Main, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universität zu Köln
🇩🇪Köln, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Klinikum rechts der Isar
🇩🇪München, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Klinikum Nürnberg
🇩🇪Nürnberg, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Universitätsklinikum Göttingen
🇩🇪Göttingen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Medizinische Universitätsklinik II
🇩🇪Tübingen, Germany