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

Myelodysplastic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01404741
• Other study ID #: VidazaAlloStudy
• Status: Completed
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: July 2021

Study information

• Verified date: October 2023
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: July 2021
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Procedure:
• allogeneic stem cell transplantation
donor available, after 4 cycles 5-azacytidine allogeneic stem cell transplantation after reduced conditioning
• 5-azacytidine until progress
if no donor available 5-azacytidine until progress or toxicities

Locations

Country	Name	City	State
Germany	Charité Campus Benjamin Franklin	Berlin
Germany	Uniklinikum Bonn	Bonn
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	Medizinische Hochschule Hannover	Hannover
Germany	Universität zu Köln	Köln
Germany	Universitätsklinikum Mannheim	Mannheim
Germany	Klinikum rechts der Isar	München
Germany	Universitätsklinikum Münster	Münster
Germany	Klinikum Nürnberg	Nürnberg
Germany	Medizinische Universitätsklinik II	Tübingen
Germany	Universitätsklinikum Ulm	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	three years
Secondary	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	three years
Secondary	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	three years
Secondary	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	three years
Secondary	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)	three years
Secondary	Treatment-related mortality	compare treatment related mortality in both arms (230 pat.): - death according to treatment in both arms	three years
Secondary	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	three years
Secondary	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	three years