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

Universitätsklinikum Hamburg-Eppendorf191 enrolled

Overview

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).

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

191

Conditions

Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia

Eligibility

Sex: ALLMin age: 55 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (17)

Charité Campus Benjamin Franklin

Berlin, Germany

Uniklinikum Bonn

Bonn, Germany

Universität zu Köln

Cologne, Germany

Universitätsklinikum Dresden

Dresden, Germany

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Universitätsklinikum Essen

Essen, Germany

Universitätsklinikum Essen

Essen, Germany

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt am Main, Germany

Universitätsklinikum Göttingen

Göttingen, Germany

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

...and 7 more locations

Outcomes

Primary Outcomes

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

Time frame: three years

Secondary Outcomes

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

Time frame: three years

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

Time frame: three years

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

Time frame: three years

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)

Time frame: three years

Treatment-related mortality

compare treatment related mortality in both arms (230 pat.): \- death according to treatment in both arms

Time frame: three years

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

Time frame: three years

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

Time frame: three years

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

Overview

Conditions

Interventions

Eligibility

Locations (17)

Outcomes

Primary Outcomes

Secondary Outcomes