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Clinical Trial Results:
Clinical phase II trial to evaluate the safety and efficacy of treosulfan combined with cytarabine and fludarabine prior to autologous haematopoietic stem cell transplantation in elderly patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.

Summary
EudraCT number	2008-000664-16
Trial protocol	IT
Global end of trial date	31 Dec 2021

Results information
Results version number	v1(current)
This version publication date	05 Feb 2026
First version publication date	05 Feb 2026
Other versions
Summary report(s)	Results_Flat_AUTO

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

FLATauto

ISRCTN number

US NCT number

NCT03961919

WHO universal trial number (UTN)

Sponsor organisation name

San Raffaele Hospital IRCCS

Sponsor organisation address

VIA OLGETTINA 60 Milano Italia, Milan, Italy, 20132

Public contact

ciceri.clinicaltrials@hsr.it, San Raffaele Hospital IRCCS Hematology and BMT Unit, +39 0226439396, ciceri.clinicaltrials@hsr.it

Scientific contact

ciceri.clinicaltrials@hsr.it, San Raffaele Hospital IRCCS Hematology and BMT Unit, +39 0226439396, ciceri.clinicaltrials@hsr.it

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

19 Jul 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

31 Dec 2019

Global end of trial reached?

Yes

Global end of trial date

31 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

Evaluation of disease free survival from first Complete Remission (CR) Evaluation of disease-free survival (DFS) duration from documented first CR of AML or MDS with intermediate 2 or high IPSS (International Prognostic Score System). [Time Frame: 2 years after transplantation]

Protection of trial subjects

Common protection due to Clinical Trial partecipant: - Pharmacovigilance - Ethical Supervision - Clincial peer reviewing

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Feb 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Italy: 15

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Versione:Livello:HLT Codice: Termine:LEUCEMIE ACUTE MIELOIDI

Screening details

Number of subjects started

Number of subjects completed

Period 1 title

Inclusion (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Treatment

Arm description

Single Group Assignment Number of Arms: 1 Masking: None (Open Label)

Arm type

Experimental

Investigational medicinal product name

FLUDARA

Investigational medicinal product code

Other name

Fludarabina

Pharmaceutical forms

Powder and solvent for dispersion for injection

Routes of administration

Solution for injection

Dosage and administration details

Concentrazione (numero): 50 Unità di concentrazione: mg milligram(s) Note: 50 mg/fiala

Investigational medicinal product name

ARACYTIN

Investigational medicinal product code

Other name

ARA-C

Pharmaceutical forms

Solution for injection

Routes of administration

Injection

Dosage and administration details

Concentrazione (numero): 50 Unità di concentrazione: mg/l milligram(s)/litre

Investigational medicinal product name

TREOSULFANO

Investigational medicinal product code

Other name

TREOSULFANO

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

Concentrazione (numero): 14 Unità di concentrazione: % percent

Investigational medicinal product name

GRANULOKINE 30

Investigational medicinal product code

Other name

Filgrastim

Pharmaceutical forms

Injection

Routes of administration

Injection

Dosage and administration details

Concentrazione (numero): 30 Unità di concentrazione: Munit million units Note: 30 MU/ML

Number of subjects in period 1	Treatment
Started	15
Completed	15

Baseline characteristics

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Reporting group title

Treatment

Reporting group description

Single Group Assignment Number of Arms: 1 Masking: None (Open Label)

Reporting group values	Treatment	Total
Number of subjects	15	15
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	0	0
From 65-84 years	15	15
85 years and over	0	0
Gender categorical
Units: Subjects
Female	9	9
Male	6	6

End points

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Reporting group title

Treatment

Reporting group description

Single Group Assignment Number of Arms: 1 Masking: None (Open Label)

Primary: Evaluation of disease free survival

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End point title

Evaluation of disease free survival ^[1]

End point description

End point type

Primary

End point timeframe

2 years after transplantation

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This is a single-arm, non-comparative study. Disease-free survival will be analysed descriptively using the Kaplan–Meier method. Median DFS and DFS rates at fixed time points with 95% confidence intervals will be reported. No formal statistical comparison between groups is planned. See PDF attached

End point values	Treatment
Number of subjects analysed	15
Units: days
number (not applicable)	454

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

day +90 after autotransplantation

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Adverse event

Reporting group description

In the population of patients aged >65 years who received at least one dose of treosulfan and underwent autologous HSCT, adverse events were collected systematically from first dose until day +90 post-transplant. All events were coded using graded according to NCI-CTC v3.0. Non-serious adverse events occurring in ≥5% of patients were reported. Extra-hematologic toxicities had a median grade of 2 (range 0–4). One patient experienced grade 4 pancytopenia resulting in death due to invasive fungal infection.

Serious adverse events	Adverse event
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 15 (66.67%)
number of deaths (all causes)	10
number of deaths resulting from adverse events	10
Nervous system disorders
Polyradiculoneuropathy
subjects affected / exposed	1 / 15 (6.67%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 1
General disorders and administration site conditions
Death
subjects affected / exposed	10 / 15 (66.67%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 10

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Adverse event
Total subjects affected by non serious adverse events
subjects affected / exposed	8 / 15 (53.33%)
Cardiac disorders
Cardiac disorder
subjects affected / exposed	3 / 15 (20.00%)
occurrences all number	1
Nervous system disorders
Neurologic Disorder
subjects affected / exposed	1 / 15 (6.67%)
occurrences all number	1
General disorders and administration site conditions
Fever
subjects affected / exposed	3 / 15 (20.00%)
occurrences all number	1
Blood and lymphatic system disorders
Extra-Hematologic toxicities
subjects affected / exposed	8 / 15 (53.33%)
occurrences all number	1
Immune system disorders
Gram negative-positive-molds
subjects affected / exposed	7 / 15 (46.67%)
occurrences all number	1
Hepatobiliary disorders
Hepatic disorder
subjects affected / exposed	3 / 15 (20.00%)
occurrences all number	1
Infections and infestations
Sepsis
subjects affected / exposed	7 / 15 (46.67%)
occurrences all number	1

More information

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Were there any global substantial amendments to the protocol? Yes

18 Jan 2018

With this non-substantial amendment, the need to extend the patient recruitment period for the protocol in question until December 2013 is being notified. This need arises from the failure to reach the planned patient sample, currently 6 out of 15, within the scheduled timeframe. The delay is mainly due both to the presence of competing allogeneic transplant protocols for the 65-70 years age group and to the frequent, sometimes fatal morbidities in patients over 70 years old during the disease treatment phases preceding this study

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Patient recruitment was slowed down both by the presence of competing allogeneic transplant protocols at the center for the 65-70 years age group and by the frequent, sometimes fatal morbidities in patients over 70 years old during the disease treatm

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Clinical trials

Clinical Trial Results:
Clinical phase II trial to evaluate the safety and efficacy of treosulfan combined with cytarabine and fludarabine prior to autologous haematopoietic stem cell transplantation in elderly patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Evaluation of disease free survival

Primary: Evaluation of disease free survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: Clinical phase II trial to evaluate the safety and efficacy of treosulfan combined with cytarabine and fludarabine prior to autologous haematopoietic stem cell transplantation in elderly patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Evaluation of disease free survival

Primary: Evaluation of disease free survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Clinical phase II trial to evaluate the safety and efficacy of treosulfan combined with cytarabine and fludarabine prior to autologous haematopoietic stem cell transplantation in elderly patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.