Feasibility of Allogeneic Stem Cell Transplantation in Higher-risk-MDS (ACROBAT)
Study Details
Study Description
Brief Summary
Open-label, randomized multicenter phase III non-inferiority study
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Open-label, randomized, prospective multicenter phase III study to compare the role of HMT followed by HSCT vs HSCT upfront in HR-MDS with <10% of BM blasts and of CHT vs HMT followed by HSCT in HR-MDS with >10% BM blasts in terms of feasibility of HSCT (non-inferiority trial).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard clinical treatment If BM-blasts >= 10%: Conventional chemotherapy: induction one cycle (3+7 protocol) and one optional consolidation cycle, followed by HSCT if a suitable sibling or unrelated donor is available versus If BM blasts are <10%: HSCT upfront |
Drug: Standard Chemotherapy
cycle (induction): i.v. 3+7 (Citarabine 200 mg/m2 iv continuous infusion (24 h) for 7 days, Daunorubicine 60 mg/mq iv day 1-3)
cycle (consolidation): i.v. 3+7 (Citarabine 200 mg/m2 iv continuous infusion (24 h) for 7 days, Daunorubicine 45 mg/mq iv day 1-3)
Other Names:
Procedure: Allogeneic stem cell transplantation
Allogeneic stem cell transplantation
Other Names:
|
| Experimental: Experimental treatment If BM-blasts >= 10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available If BM blasts are <10%: Azacitidine (AZA) 75mg/sqm/day subcutaneously for 7 days every 28 days (1 cycle of 28 days) for at least 4 cycles, followed by HSCT if a suitable sibling or unrelated donor is available |
Drug: Azacitidine
75mg/mq/day subcutaneously for 7 days every 28 days
Other Names:
Procedure: Allogeneic stem cell transplantation
Allogeneic stem cell transplantation
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Feasibility of HSCT in terms of proportion of patients who receive HSCT of the total number of randomized patients [4 years]
Split patients 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%.
Eligibility Criteria
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
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HSCT - eligible
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Life expectancy ≥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:
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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);
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severe renal, cardiac, liver or lung impairment;
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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;
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hypersensitivity (known or suspected) to AZA;
-
prior Treatments:
-
prior investigational drugs (within 30 days);
-
radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months;
-
growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days;
-
androgenic hormones during the previous 14 days;
-
prior transplantation or cytotoxic therapy, including azacitidine, AZA or chemotherapy, administered to treat MDS (a previous treatment with Lenalidomide is admitted, provided that lenalidomide had been stopped at least 60 days before enrolment).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDS 0519