AZACITIDINE for Myelodysplastic syndrome (high-risk)

Stratification factors

• Bone marrow blast proportion (<10% vs >=10%)

Inclusion criteria

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

Exclusion criteria

• {"criterion_text":"- Acute myeloid leukaemia with >20% blasts in BM or peripheral blood (PB)"}
• {"criterion_text":"- concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma)"}
• {"criterion_text":"- severe renal, cardiac, liver or lung impairment"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- HIV infection; active, uncontrolled HCV or HBV infections or liver cirrhosis"}
• {"criterion_text":"- clinically relevant neurological or psychiatric diseases"}
• {"criterion_text":"- hypersensitivity (known or suspected) to AZA"}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Feasibility estimated as the proportion of randomized patients who receive HSCT; patients who perform HSCT counted as 'successes' and others as 'failures'. Sensitivity analyses adjusting for prognostic factors will be performed."}

Secondary endpoints

• {"endpoint_text":"- Overall survival ITT","definition_or_measurement_approach":"Overall survival measured in the intention-to-treat population."}
• {"endpoint_text":"- Event-free survival ITT (including relapse, progression, or death from any cause)","definition_or_measurement_approach":"Event-free survival in the ITT population, events include relapse, progression, or death from any cause."}
• {"endpoint_text":"- Safety in terms of AE/SAEs","definition_or_measurement_approach":"Safety assessed by recording adverse events (AEs) and serious adverse events (SAEs)."}
• {"endpoint_text":"- Pattern of relapse/progression after HSCT","definition_or_measurement_approach":"Descriptive assessment of relapse/progression patterns following HSCT."}
• {"endpoint_text":"- Translational studies with mutational, and cytofluorimetric analysis (patient BM-sampling at enrollment, before HSCT and at 6 months after HSCT)","definition_or_measurement_approach":"Translational analyses including mutational and cytofluorimetric tests on bone marrow samples at enrollment, pre-HSCT, and 6 months post-HSCT."}
• {"endpoint_text":"- Quality of life assessment at enrollment, before HSCT and at 6 months after HSCT","definition_or_measurement_approach":"Quality of life measured at specified timepoints (enrollment, pre-HSCT, 6 months post-HSCT) using QoL instruments (not further specified)."}
• {"endpoint_text":"- Pharmacoeconomic evaluation (i.e. duration of hospitalization, RBC transfusions, etc)","definition_or_measurement_approach":"Pharmacoeconomic outcomes including duration of hospitalization and red blood cell transfusions."}

Italy

Earliest CTIS Part Ii Submission Date

22-12-2023

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

614

Number Of Participants

274

Primary sponsor

Full Name

Fondazione Gimema Franco Mandelli Onlus

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Laboratorio di Diagnostica Integrata Oncoematologica “OPPO”","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Health care"}