Prospective randomized study on the feasibility of allogeneic stem cell transplantation in higher-risk-myelodysplastic syndromes, performed upfront or preceded by azacitidine or conventional chemotherapy, according to the BM-blast proportion (ACROBAT trial). MDS0519

Fondazione Gimema Franco Mandelli Onlus, Fondazione Gimema Franco Mandelli Onlus46 sites in 1 country274 target enrollmentJuly 30, 2024

DrugsCYTARABINE THIOTEPA Azacitidine Accord 25 mg/mL powder for suspension for injection FLUDARABINE PHOSPHATE BUSULFAN DAUNORUBICIN HYDROCHLORIDE

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Not specified
Sponsor: Fondazione Gimema Franco Mandelli Onlus, Fondazione Gimema Franco Mandelli Onlus
Enrollment: 274
Locations: 46
Primary Endpoint: Feasibility of HSCT- Non-inferiority design. The feasibility of HSCT will be estimated in terms of proportion of patients who receive HSCT of the total number of randomized patients. For the primary endpoint of feasibility of HSCT, all patients who perform HSCT will be considered as "successes", and all others, as "failures". For the primary efficacy endpoint, sensitivity analyses will be performed adjusting the treatment comparison by factors which appeared to be of prognotic importance
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of this study has been split in two categories: the feasibility of HSCT (ITT) in patients with HR-MDS with a proportion of bone marrow blasts below 10% and in patients with a proportion of BM blasts equal or greater than 10%.

Registry

euclinicaltrials.eu

Start Date

July 30, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Fondazione Gimema Franco Mandelli Onlus, Fondazione Gimema Franco Mandelli Onlus

Responsible Party

Principal Investigator

Data center

Scientific

Fondazione Gimema Franco Mandelli Onlus

Eligibility Criteria

Inclusion Criteria

•Patients with newly diagnosed higher-risk MDS, including IPSS Intermediate-2 and high, and IPSS-R intermediate to very-high
•Age 18-70 years
•Previously untreated for HR-MDS
•HSCT – eligible
•Life expectancy greater than or equal to 3 months
•Signed written informed consent according to ICH/EU/GCP and national local laws
•Eastern Cooperative Oncology Group Performance Status Grade of 0-2

Exclusion Criteria

•Acute myeloid leukaemia with >20% blasts in BM or peripheral blood (PB)
•concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma)
•severe renal, cardiac, liver or lung impairment
•pregnant or lactating or potentially fertile (both males and females), who have not agreed to avoid pregnancy during the trial period; Women of childbearing potential and men must agree to use effective contraception during and up to 3 months after treatment with azacitidine.
•HIV infection; active, uncontrolled HCV or HBV infections or liver cirrhosis
•clinically relevant neurological or psychiatric diseases
•hypersensitivity (known or suspected) to AZA
•prior Treatments: a) prior investigational drugs (within 30 days); b) radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months; c) growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days; d) androgenic hormones during the previous 14 days; e) prior transplantation or cytotoxic therapy, including azacitidine, AZA or chemotherapy, administered to treat MDS.

Outcomes

Primary Outcomes

Feasibility of HSCT- Non-inferiority design. The feasibility of HSCT will be estimated in terms of proportion of patients who receive HSCT of the total number of randomized patients. For the primary endpoint of feasibility of HSCT, all patients who perform HSCT will be considered as "successes", and all others, as "failures". For the primary efficacy endpoint, sensitivity analyses will be performed adjusting the treatment comparison by factors which appeared to be of prognotic importance

Secondary Outcomes

Overall survival ITT
Event-free survival ITT (including relapse, progression, or death from any cause)
Safety in terms of AE/SAEs
Pattern of relapse/progression after HSCT
Translational studies with mutational, and cytofluorimetric analysis (patient BMsampling at enrollment, before HSCT and at 6 months after HSCT)
Quality of life assessment at enrollment, before HSCT and at 6 months after HSCT
Pharmacoeconomic evaluation (i.e. duration of hospitalization, RBC transfusions, etc)