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

Phase 3

Recruiting

• Conditions: High-risk MDS
• Interventions: Drug: Standard Chemotherapy; Drug: Azacitidine; Procedure: Allogeneic stem cell transplantation

• Registration Number: NCT04184505
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

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).

Study Timeline

• Study First Submitted: 2019-11-29
• Study First Submitted QC: 2019-11-29
• Study First Posted: 2019-12-03
• Study Start: 2020-11-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-03-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 274

Inclusion Criteria

1. Patients with newly diagnosed higher-risk MDS, including IPSS Intermediate-2 and high, and IPSS-R intermediate to very-high
2. Age 18-70 years
3. Previously untreated for HR-MDS
4. HSCT - eligible
5. Life expectancy ≥3 months;
6. Signed written informed consent according to ICH/EU/GCP and national local laws
7. Eastern Cooperative Oncology Group Performance Status Grade of 0-2

Exclusion Criteria

1. Acute myeloid leukaemia with >20% blasts in BM or peripheral blood (PB);

2. concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma);

3. severe renal, cardiac, liver or lung impairment;

4. 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.

5. HIV infection; active, uncontrolled HCV or HBV infections or liver cirrhosis;

6. clinically relevant neurological or psychiatric diseases;

7. hypersensitivity (known or suspected) to AZA;

8. prior Treatments:

   1. prior investigational drugs (within 30 days);
   2. radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months;
   3. growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days;
   4. androgenic hormones during the previous 14 days;
   5. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental treatment	Allogeneic stem cell transplantation	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
Standard clinical treatment	Allogeneic stem cell transplantation	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
Standard clinical treatment	Standard Chemotherapy	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
Experimental treatment	Azacitidine	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

Primary Outcome Measures

Name	Time	Method
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%.

Trial Locations

Locations (46)

Aso S. Croce E Carle - Sc Ematologia; 🇮🇹 Cuneo, Italy

Aou Ospedali Riuniti- Uoc Ematologia; 🇮🇹 Foggia, Italy

Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo; 🇮🇹 Napoli, Italy

Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia; 🇮🇹 Orbassano, Italy

058 - Aon Ss. Antonio E Biagio E C. Arrigo - Soc Ematologia; 🇮🇹 Alessandria, Italy

Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi - Sod Clinica Ematologica; 🇮🇹 Ancona, Italy

Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia; 🇮🇹 Ascoli Piceno, Italy

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto; 🇮🇹 Bari, Italy

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia; 🇮🇹 Bologna, Italy

Asst Degli Spedali Civili Di Brescia - Uo Ematologia; 🇮🇹 Brescia, Italy

Asl Brindisi, Ospedale 'Perrino'- Uo Ematologia; 🇮🇹 Brindisi, Italy

U.O.C. Oncoematologia - Istituto Oncologico Veneto Irccs - Presidio Ospedaliero S. Giacomo Apostolo; 🇮🇹 Castelfranco Veneto, Italy

Aou Policlinico Vittorio Emanuele, Po Ospedaliero "G. Rodolico" - Uo Ematologia Con Trapianto Di Midollo Osseo; 🇮🇹 Catania, Italy

Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione; 🇮🇹 Cona, Italy

Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia; 🇮🇹 Latina, Italy

Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia; 🇮🇹 Lecce, Italy

Aulss 3 Serenissima, Ospedale Dell'Angelo Uo Ematologia; 🇮🇹 Mestre, Italy

Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia; 🇮🇹 Milano, Italy

Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia; 🇮🇹 Milano, Italy

Aou Di Modena - Sc Ematologia; 🇮🇹 Modena, Italy

Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia; 🇮🇹 Pagani, Italy

Aou Policlinico P. Giaccone - Uo Ematologia; 🇮🇹 Palermo, Italy

Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica; 🇮🇹 Pescara, Italy

Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti; 🇮🇹 Piacenza, Italy

Aou Pisana - Uo Ematologia Universitaria; 🇮🇹 Pisa, Italy

Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia; 🇮🇹 Reggio Calabria, Italy

Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia; 🇮🇹 Reggio Emilia, Italy

Ausl Della Romagna, Ospedale "Infermi" - Uo Ematologia; 🇮🇹 Rimini, Italy

Ao Complesso Ospedaliero San Giovanni / Addolorata - Roma - Uoc Ematologia; 🇮🇹 Roma, Italy

Ao San Camillo Forlanini Uoc Ematologia E Trapianto Cellule Staminali; 🇮🇹 Roma, Italy

Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali; 🇮🇹 Roma, Italy

Aou Sant'Andrea - Roma - Uoc Ematologia; 🇮🇹 Roma, Italy

Asl Roma 2, Ospedale S. Eugenio- Uoc Ematologia; 🇮🇹 Roma, Italy

Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica; 🇮🇹 Roma, Italy

Istituti Fisioterapici Ospitalieri - Ifo - Istituto Regina Elena - Roma - Uosd Ematologia; 🇮🇹 Roma, Italy

Policlinico Universitario Campus Bio Medico - Roma - Uoc Ematologia E Trapianto Di Cellule Staminali; 🇮🇹 Roma, Italy

Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia; 🇮🇹 Roma, Italy

Aou "San Giovanni Di Sio E Ruggi D'Aragona" - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche; 🇮🇹 Salerno, Italy

Aou Di Sassari - Cliniche Universitarie - Stabilimento Cliniche Di San Pietro - Uoc Ematologia; 🇮🇹 Sassari, Italy

Aou Senese - Uoc Ematologia E Trapianti; 🇮🇹 Siena, Italy

Aou Citta' Della Salute E Della Scienza - Osp. S. Giovanni Battista Molinette - Sc Ematologia 2; 🇮🇹 Torino, Italy

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino; 🇮🇹 Torino, Italy

ENTE ECCLESIASTICO CARDINALE G. PANICo - UO EMATOLOGIA; 🇮🇹 Tricase, Italy

Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica; 🇮🇹 Udine, Italy

Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia; 🇮🇹 Verona, Italy

Asl Di Viterbo, Complesso Ospedaliero Di Belcolle - Uoc Ematologia; 🇮🇹 Viterbo, Italy