The study is aimed at evaluating the feasibility of a hypomethylating treatment combined with hematopoietic stem cell transplantation in comparison to hematopoietic stem cell transplantation in patients with high-risk myelodysplastic syndrome.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

27 Nov 2020 → ongoing

Decision date (initial)

2024-07-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AIFA · Fondazione GIMEMA Franco Mandelli ONLUS

External identifiers

EU CT number

2023-510515-19-00

EudraCT number

2019-003997-25

ClinicalTrials.gov

NCT04184505

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Therapy, Efficacy

The primary objective of this study has been split 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%.

Secondary objectives 8

1. Overall survival ITT
2. Event-free survival ITT (including relapse, progression, or death from any cause)
3. Safety
4. Changes in HCT-CI at the time of HSCT as compared to the time of enrollment
5. Pattern of relapse/progression after HSCT
6. Translational studies with pre- and post-treatment mutational, methylation and cytofluorimetric analysis (patient BM-sampling at enrollment, before HSCT and at 6 months after HSCT)
7. Quality of life assessment at enrollment, before HSCT and at 6 months after HSCT
8. Pharmacoeconomic evaluation in terms of duration of hospitalization

Conditions and MedDRA coding

Higher-risk-myelodysplastic syndromes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 greater than or equal to 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 8

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: a) prior investigational drugs (within 30 days); b) radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months; c) growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days; d) androgenic hormones during the previous 14 days; e) prior transplantation or cytotoxic therapy, including azacitidine, AZA or chemotherapy, administered to treat MDS.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Feasibility of HSCT- Non-inferiority design. The feasibility of HSCT will be estimated in terms of proportion of patients who receive HSCT of the total number of randomized patients. For the primary endpoint of feasibility of HSCT, all patients who perform HSCT will be considered as "successes", and all others, as "failures". For the primary efficacy endpoint, sensitivity analyses will be performed adjusting the treatment comparison by factors which appeared to be of prognotic importance

Secondary endpoints 7

1. Overall survival ITT
2. Event-free survival ITT (including relapse, progression, or death from any cause)
3. Safety in terms of AE/SAEs
4. Pattern of relapse/progression after HSCT
5. Translational studies with mutational, and cytofluorimetric analysis (patient BMsampling at enrollment, before HSCT and at 6 months after HSCT)
6. Quality of life assessment at enrollment, before HSCT and at 6 months after HSCT
7. Pharmacoeconomic evaluation (i.e. duration of hospitalization, RBC transfusions, etc)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Third parties 1

Locations

1 EU/EEA country · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications