Clinical trial NCT01404741: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Keywords: MDS
CMML
allogeneic stem cell transplantation
5-azacytidine
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2011-07-28
Enrollment: 191
Sex: ALL
Minimum age (years): 55
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: overall survival
timeFrame: three years
Secondary outcomes:
measure: response
timeFrame: three years
measure: event-free survival
timeFrame: three years
measure: overall survival
timeFrame: three years
measure: impact of Comorbidity-index on outcome
timeFrame: three years
measure: Treatment-related mortality
timeFrame: three years
measure: Evaluation of toxicity
timeFrame: three years
measure: quality of life
timeFrame: three years
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Bonn
country: Germany
facility: Uniklinikum Bonn
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Universität zu Köln
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Tübingen
country: Germany
facility: Medizinische Universitätsklinik II
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: University Medical Centre Hamburg-Eppendorf, Stem-Cell-Transplantation
name: Nicolaus Kroeger, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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.