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

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase: Enrolling; Phase 3

Conditions: High-risk MDS

Treatments: Drug: Azacitidine; Drug: Standard Chemotherapy; Procedure: Allogeneic stem cell transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT04184505

MDS0519

Details and patient eligibility

About

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

Full 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).

Enrollment: 274 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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274 participants in 2 patient groups

Standard clinical treatment

Active Comparator group

Description:

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

Treatment:

Procedure: Allogeneic stem cell transplantation

Drug: Standard Chemotherapy

Experimental treatment

Experimental group

Description:

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

Treatment:

Procedure: Allogeneic stem cell transplantation

Drug: Azacitidine