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

High-risk MDS Clinical Trial

— ACROBAT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04184505
• Other study ID #: MDS 0519
• Status: Recruiting
• Phase: Phase 3
• Start date: November 27, 2020
• Est. completion date: March 1, 2024

Study information

• Verified date: October 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, randomized multicenter phase III non-inferiority study

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 274
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• High-risk MDS

Intervention

Drug:
• Azacitidine
75mg/mq/day subcutaneously for 7 days every 28 days
• 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)

Procedure:
• Allogeneic stem cell transplantation
Allogeneic stem cell transplantation

Locations

Country	Name	City	State
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 Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia	Latina
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	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	Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica	Pescara
Italy	Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli" Po E. Morelli - Reggio Calabria - Uoc Ematologia	Reggio Calabria
Italy	Ao Complesso Ospedaliero San Giovanni / Addolorata - Roma - Uoc Ematologia	Roma
Italy	Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali	Roma
Italy	Aou Sant'Andrea - Roma - 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	Aou Di Sassari - Cliniche Universitarie - Stabilimento Cliniche Di San Pietro - Uoc Ematologia	Sassari
Italy	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino	Torino
Italy	Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica	Udine

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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