Clinical Trials Register

Summary
EudraCT Number:	2017-003530-85
Sponsor's Protocol Code Number:	GITMO-PHYLOS
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-14
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-003530-85

A.3

Full title of the trial

Post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Cell Transplantation for Myeloid Malignancies

Alte dosi di Ciclofosfamide post trapianto come profilassi per la GvHD, in pazienti sottoposti a trapianto di cellule staminali emopoietiche da donatore non familiare, non HLA identico (7/8 antigene o allele), affetti da Leucemia Mieloide Acuta o da Sindrome Mielodisplastica.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

High doses of cyclophosphamide for prophylaxis of GVHD in patients undergoing allogeneic transplantation

Alte dosi di ciclofosfamide per la profilassi della GVHD in pazienti sottoposti a trapianto allogenico

A.3.2

Name or abbreviated title of the trial where available

GITMO-PHYLOS

A.4.1

Sponsor's protocol code number

GITMO-PHYLOS

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03270748

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GITMO GRUPPO ITALIANO PER IL TRAPIANTO DI MIDOLLO OSSEO, CELLULE STAMINALI EMOPOIETICHE E TERAPIA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	gitmo
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GITMO
B.5.2	Functional name of contact point	TRIALS OFFICE GITMO
B.5.3	Address:
B.5.3.1	Street Address	c/o ospedale Policlinico San Martino, Pad. 6, Largo R. Benzi 10
B.5.3.2	Town/ city	GENOVA
B.5.3.3	Post code	16132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0105554423
B.5.5	Fax number	010515491
B.5.6	E-mail	sonia.mammoliti@hsanmartino.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	BUSILVEX - 6 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO - 10 ML 8 FLACONCINI
D.2.1.1.2	Name of the Marketing Authorisation holder	PIERRE FABRE MEDICAMENT
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Busulfano
D.3.2	Product code	[Busulfano]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BUSULFANO
D.3.9.2	Current sponsor code	busulfano
D.3.9.3	Other descriptive name	busulfan
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	FLUDARABINA TEVA - 25 MG/ML CONCENTRATO PER SOLUZIONE INIETTABILE O PER INFUSIONE 1 FLACONCINO DI VETRO DA 2 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fludarabina
D.3.2	Product code	[Fludarabina]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUDARABINA
D.3.9.2	Current sponsor code	Fludarabina
D.3.9.3	Other descriptive name	Fludarabine
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ENDOXAN BAXTER - 200 MG POLVERE PER SOLUZIONE INIETTABILE 10 FLACONI VETRO TIPO III 200 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	BAXTER S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ciclofosfamide
D.3.2	Product code	[Ciclofosfamide]
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CICLOFOSFAMIDE
D.3.9.2	Current sponsor code	Ciclofosfamide
D.3.9.3	Other descriptive name	Cyclophosphamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SANDIMMUN - 50 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 10 FIALE 5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS EUROPHARM LTD
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ciclosporina
D.3.2	Product code	[Ciclosporina]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CICLOSPORINA
D.3.9.2	Current sponsor code	Ciclosporina
D.3.9.3	Other descriptive name	Cyclosporine
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SANDIMMUN - 25 MG CAPSULE MOLLI 50 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS EUROPHARM LTD
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ciclosporina
D.3.2	Product code	[Ciclosporina]
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CICLOSPORINA
D.3.9.2	Current sponsor code	Ciclosporina
D.3.9.3	Other descriptive name	Cyclosporine
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	PROGRAF - 5 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 10 FIALE 1 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTELLAS PHARMA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tacrolimus
D.3.2	Product code	[Tacrolimus]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TACROLIMUS
D.3.9.2	Current sponsor code	Tacrolimus
D.3.9.3	Other descriptive name	Tacrolimus
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 7
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	MICOFENOLATO MOFETILE ACCORD - 250 MG CAPSULE RIGIDE 100 CAPSULE IN BLISTER PVC/PVDC/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Micofenolato mofetile
D.3.2	Product code	[Micofenolato mofetile]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MICOFENOLATO MOFETILE
D.3.9.2	Current sponsor code	Micofenolato mofetile
D.3.9.3	Other descriptive name	Mycophenolate Mofetil
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute myeloid leukemia or myelodysplastic syndrome undergoing 1 antigen/allele mismatched (7/8 HLA matched) unrelated HCT

Leucemia Mieloide Acuta in remissione o da Sindrome Mielodisplastica sottoposti a trapianto di cellule staminali emopoietiche da donatore non familiare non HLA identico (7/8 a livello antigenico o allelico).

E.1.1.1

Medical condition in easily understood language

Patients with Acute Myeloid Leukemia in remission or Myelodysplastic Syndrome candidates for allogeneic transplantation

Pazienti con Leucemia Mieloide Acuta in remissione o da Sindrome Mielodisplastica candidati al trapianto allogenico

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10068372
E.1.2	Term	Prophylaxis against stem cell transplant rejection
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10000880
E.1.2	Term	Acute myeloid leukaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028533
E.1.2	Term	Myelodysplastic syndrome
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective is to reduce the incidence of acute GvHD (grade II-IV) after 1 antigen/allele mismatched (7/8 HLA matched) unrelated hematopoietic cell transplantation (HCT) using post-transplant high-dose cyclophosphamide in patients with myeloid malignancies.

L’obiettivo primario è la riduzione della graft-versus-host disease (GvHD) acuta (grado II-IV) dopo trapianto di cellule staminali emopoietiche allogeniche da donatore non familiare, non HLA identico (7/8 antigene o allele) in pazienti affetti da leucemia mieloide acuta o mielodisplasia, utilizzando le alte dosi di Ciclofosfamide post trapianto come profilassi.

E.2.2

Secondary objectives of the trial

Secondary Objectives are safety and efficacy of post-transplant high-dose cyclophosphamide after 1 antigen/allele mismatched unrelated HCT defined as:
Overall survival (OS)
Probability of GRFS (GvHD free, relapse free survival)
Incidence and severity of chronic GvHD.
Incidence of graft failure
Time to haematological reconstitution (neutrophil and platelet recovery)
Incidence of Non-Relapse Mortality (NRM)
Incidence and time of disease relapse
Incidence of infectious complications and time to immune-reconstitution
Incidence of endothelial complications (in particularly sinusoidal obstruction syndrome/veno-occlusive disease).

Sicurezza ed efficacia post trapianto definiti come:
Sopravvivenza globale (OS)
Probabilità di GRFS (sopravvivenza libera da recidiva e da GvHD)
Incidenza e severità della GvHD cronica
Incidenza di mancato attecchimento
Ricostituzione ematologica di neutrofili e piastrine
Incidenza della Non-Relapse Mortality (NRM).
Incidenza e tempi della recidiva di malattia
Incidenza delle complicanze infettive e tempi della ricostituzione immunologica
Incidenza delle complicanze endoteliali con particolare attenzione alla diagnosi di SOS/VOD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients >18 <65 years of age
Diagnosis of acute myeloid leukemia in complete remission (CR1, CR2) or myelodysplastic syndrome with indication for allo-HCT
No available HLA identical sibling donor or HLA matched (8/8) unrelated donor
Activation of an alternative donor search through IBMDR
Presence of a 1 antigen/allele mismatched (7/8 HLA matched) unrelated donor (loci: HLA-A, -B, -C, - DRB1)
ECOG Performance Status < 2
Written and signed informed consent.

Età >18 <65
Diagnosi di leucemia mieloide acuta in remissione completa (CR1 o CR2) o sindrome mielodisplastica con indicazione al trapianto di cellule staminali emopoietiche allogeniche.
Indisponibilità di donatore familiare o di donatore non familiare HLA identico (8/8)
Attivazione della ricerca per un donatore non familiare nel registro IBMDR
Disponibilità di un donatore non familiare non HLA identico (7/8 a livello allelico o antigenico) (loci: HLA- A, -B, -C, - DRB1)
Performance status: ECOG < 2
Consenso informato firmato

E.4

Principal exclusion criteria

Previous allogeneic HCT (autologous HCT is accepted)
Absence of informed consent
Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) <40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min.

Precedente trapianto allogenico (precedente trapianto autologo è consentito)
Assenza di consenso Informato
Importanti disfunzioni d’organo: frazione di eiezione del ventricolo sinistro <40%, FEV1, FVC, DLCO <40% of predicted, LFT >5 volte superiore al limite di normalità, o clearance della creatinina <40ml/min.

E.5 End points

E.5.1

Primary end point(s)

Primary outcome is the cumulative incidence of acute GvHD (grade II-IV)

L'enpoint primario è l’incidenza cumulativa di GvHD acuta (grado II-IV)

E.5.1.1

Timepoint(s) of evaluation of this end point

at 100 days after unrelated transplant graded according to the Glucksberg scale.

a 100 giorni dopo trapianto non correlato classificato secondo la scala di Glucksberg.

E.5.2

Secondary end point(s)

Chronic graft-versus-host disease (cGvHD); Overall survival (OS); GRFS (GvHD free, relapse free survival); Graft failure; Time to neutrophil and platelet recovery; The cumulative incidence of Non Relapse Mortality (NRM); Relapse and Residual Disease; Incidence of infectious complications and kinetics of immune-reconstitution; Cumulative incidence of endothelial complications

malattia del trapianto contro l'ospite cronica (cGvHD); Sopravvivenza globale (OS); GRFS (liberi da GvHD, sopravvivenza senza ricaduta); Fallimento dell'attecchimento; Tempo di ricostituzione ematologica; Incidenza cumulativa della mortalità senza ricaduta (NRM); Recidiva e malattia residua; Incidenza di complicanze infettive e cinetica della ricostituzione immunitaria; Incidenza cumulativa delle complicanze endoteliali

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year post transplant; at 1 year post transplant; 1 year post transplant; at day +100 and at 1 year after transplantation; at day +30 and +100 post transplant; at day +100, day +180 and at 1 year post transplant; at 1 year after transplantation; one year after transplant; within 100 days from transplant according to EBMT criteria

1 anno post trapianto; a 1 anno post trapianto; 1 anno post trapianto; al giorno +100 e ad 1 anno post trapianto; al giorno +30 e +100 post trapianto; ai giorni +100, +180 e 1 anno post-trapianto; ad 1 anno post trapianto; 1 anno post trapianto; entro 100 giorni dal trapianto in accordo ai Criteria EBMT

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

NONE

NESSUNO

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-29

P. End of Trial
P.	End of Trial Status	Ongoing

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