Feasibility of Allogeneic Stem Cell Transplantation in Higher-risk-MDS (ACROBAT)

Study Overview
=================
Brief Summary
-----------------
Open-label, randomized multicenter phase III non-inferiority study

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).

Official Title
-----------------
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

Conditions
-----------------
High-risk MDS

Intervention / Treatment
-----------------
* Drug: Azacitidine
* Drug: Standard Chemotherapy
* Procedure: Allogeneic stem cell transplantation


Participation Criteria
=================
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 ≥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: 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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard clinical treatment<br>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<br>* 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)<br>* Other names: STD CHT;Procedure: Allogeneic stem cell transplantation<br>* Allogeneic stem cell transplantation<br>* Other names: HSCT;|
| Experimental: Experimental treatment<br>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<br>* 75mg/mq/day subcutaneously for 7 days every 28 days<br>* Other names: AZA;Procedure: Allogeneic stem cell transplantation<br>* Allogeneic stem cell transplantation<br>* Other names: HSCT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of HSCT in terms of proportion of patients who receive HSCT of the total number of randomized patients | 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%. | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MDS, Transplant, Azacitidine