Clinical Trials Register

Summary
EudraCT Number:	2020-005902-24
Sponsor's Protocol Code Number:	ONC-2020-001
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:	2021-06-08
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

2020-005902-24

A.3

Full title of the trial

Phase II Clinical Trial to optimize the dose of an anti-NKG2A monoclonal antibody (humZ270 mAb, IPH2201) for patients with acute myeloid leukemia or myelodysplastic syndrome undergoing haploidentical transplantation with posttransplantation cyclophosphamide.

Studio clinico di fase II per ottimizzare la dose di un anticorpo monoclonale anti-NKG2A (humZ270 mAb, IPH2201) per pazienti con leucemia mieloide acuta o sindrome mielodisplastica che ricevono un trapianto aploidentico con ciclofosfamide post-trapianto.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

ONC-2020-001

A.4.1

Sponsor's protocol code number

ONC-2020-001

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	IRCCS ISTITUTO CLINICO HUMANITAS
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	Associazione AIRC nell’ambito del Bando Investigator Grant per l’anno 2018
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	IRCCS Istituto Clinico Humanitas
B.5.2	Functional name of contact point	Data Manager U.O Ematologia
B.5.3	Address:
B.5.3.1	Street Address	Via Alessandro Manzoni, 56
B.5.3.2	Town/ city	Rozzano (MI)
B.5.3.3	Post code	20089
B.5.3.4	Country	Italy
B.5.4	Telephone number	0282244081
B.5.5	Fax number	0282244591
B.5.6	E-mail	elisa.carra@humanitas.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	No
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	Monalizumab
D.3.2	Product code	[IPH2201]
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection/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	Monalizumab
D.3.9.1	CAS number	1228763-95-8
D.3.9.2	Current sponsor code	IPH2201
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	375
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

Patients with acute myeloid leukemia or myelodysplastic syndrome undergoing haploidentical transplantation with posttransplantation cyclophosphamide.

Pazienti con leucemia mieloide acuta o sindrome mielodisplastica che ricevono un trapianto aploidentico con ciclofosfamide post-trapianto.

E.1.1.1

Medical condition in easily understood language

Patients with acute myeloid leukemia or myelodysplastic syndrome.

Pazienti con leucemia mieloide acuta o sindrome mielodisplastica.

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	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

Evaluate the efficacy and safety of Monalizumab after Haplo-SCT with PT-Cy.

Valutare l’efficacia e la sicurezza della somministrazione di Monalizumab dopo Haplo-SCT con PT-Cy.

E.2.2

Secondary objectives of the trial

Evaluate the effect of monalizumab on the immunological reconstitution and other clinical parameters of survival and toxicity.

Valutare l’effetto del farmaco sulla ricostituzione immunologica e su altri parametri clinici di sopravvivenza e di tossicità.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Patients capable of providing informed consent according to ICH/ GCP, and national/local regulations and be willing to comply with all study-related procedures.
2) Adult patients aged =18 years and =70 years old, without any restriction of gender and race.
3) Patients with a hematologic malignancy represented either by Acute Myeloid Leukemia or Myelodysplastic Syndrome (MDS).
4) Patients lacking a human leukocyte antigen (HLA) identical donor and receiving Haplo-SCT with GVHD/host versus graft (HVG) prophylaxis consisting of Cyclophosphamide: 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5, Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +35.
5) Patient who have received Haplo-SCT with a myeloablative (MA) or reduced intensity (RIC) or non-myeloblative (NMA) conditioning followed either by a bone marrow or a peripheral blood stem cell (PBSC) graft.
6) Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential.
7) Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the last dose of study therapy.
Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 52 weeks after the patient receives his last dose of study therapy contraception.

1) Pazienti in grado di fornire il proprio consenso informato in accordo alle linee guida ICH/ GCP e al regolamento locale, e di acconsentire all’esecuzione di tutte le procedure di studio.
2) Pazienti adulti con età compresa tra i 18 e 70 anni di età compresi, senza restrizioni di genere e razza.
3) Pazienti affetti da una neoplasia ematologica rappresentata da Leucemia Mieloide Acuta o Sindrome Mielodisplastica.
4) Pazienti senza un donatore HLA-identico e che hanno ricevuto un trapianto di cellule staminali aploidentico con la seguente profilassi per GVHD/HVG: 50 mg/kg/die nei giorni +3 e +4, Ciclosporina A: 3 mg/kg/die dal giorno +5, Micofenolato mofetile: 45 mg/kg/die, dal giorno +5 al giorno +35.
5) Pazienti che hanno ricevuto un trapianto di cellule staminali aploidentico da midollo o da cellule staminali da sangue periferico con condizionamento mieloablativo, a ridotta intensità o non mieloablativo.
6) Test di gravidanza negativo (gonadotropina corionica beta umana, ß-HCG) entro i 7 giorni precedenti l’inizio della terapia sperimentale per le donne fertili.
7) Le donne fertili devono acconsentire all’uso di un metodo contraccettivo altamente efficace dal momento in cui firma il consenso informato per lo studio fino a 52 settimane dall’ultima dose di farmaco sperimentale ricevuta.
I pazienti maschi con partner fertili devono acconsentire all’utilizzo di un metodo contraccettivo altamente efficace dal momento in cui firmano il consenso per lo studio fino a 52 settimane dall’ultima dose di farmaco sperimentale ricevuta.

E.4

Principal exclusion criteria

1) Patients aged < 18 or > 70 years old.
2) Active uncontrolled infections.
3) Central nervous system (CNS) involvement of AML disease.
4) Karnofsky performance status (KPS) <60% or severe organ dysfunction, including a left ventricular ejection fraction <40%, DLCO <50% or creatinine clearance <50 ml/min (as per transplant eligibility).
5) Pregnant or breast-feeding or intending to become pregnant during the study.
6) Patients who rapidly relapse after allogenic-SCT before day 30 after Haplo-SCT.
7) Patients who experience acute GVHD before day +30 after Haplo-SCT.
8) Patients treated with a second allogeneic Allo-SCT.

1) Pazienti con età inferiore a 18 anni o maggiore di 70 anni.
2) Infezioni attive non controllate.
3) Coinvolgimento del sistema nervoso centrale della leucemia mieloide acuta.
4) Performance status secondo la scala di Karnofsky <60% o con disfunzione d’organo severa, tra cui frazione di eiezione ventricolare sinistra <40%; DLCO <50%, clearance della creatinina <50 ml/min (come da eligibilità per il trapianto allogenico).
5) Donne incinte o in allattamento o che intendono rimanere incinta per l’intera durata di studio.
6) Pazienti con progressione della malattia ematologica comparsa nei 30 giorni successivi al trapianto aploidentico.
7) Pazienti con malattia da rigetto (GVHD) comparsa prima del giorno +30 post trapianto aploidentico.
8) Pazienti che hanno ricevuto un secondo trapianto allogenico aploidentico di cellule staminali.

E.5 End points

E.5.1

Primary end point(s)

To evaluate the efficacy and safety of NKG2A blockade by Monalizumab after Haplo-SCT with PTCy in terms of GPFS.

Valutare la GPFS (graft versus host disease free and progression free survival) ad 1 anno dopo Haplo-SCT.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year.

1 anno.

E.5.2

Secondary end point(s)

Clinical Objectives: Evaluate the incidence of OS, PFS, NRM and post-transplant viral infections in patients receiving Monalizumab after Haplo-SCT.
Biological Objectives: Evaluate the reconstitution and alloreactive functions of NK cell population against leukemic cells after Monalizumab administration.

Obiettivi clinici: valutare l’incidenza di OS (Overall Survival), PFS (Progression Free Survival), NRM (Non-Relapse Mortality), di infezioni virali post-trapianto, di GVHD acuta e cronica.
Obiettivi Biologici: valutare la ricostituzione e le funzioni alloreattive della popolazione delle cellule NK contro cellule di LMA dopo l’infusione dell’anticorpo anti-NKG2A.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year.

1 anno.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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)

n.a.

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

2021-06-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-15

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

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