Clinical Trials Register

Summary
EudraCT Number:	2020-005025-85
Sponsor's Protocol Code Number:	FT03CARCIK
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:	2021-06-04
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

2020-005025-85

A.3

Full title of the trial

Measurable residual disease driven strategy for one or two infusions of non-viral, transposon-manipulated CARCIK-CD19 cells. A Phase II study in pediatric and adult patients with relapsed/refractory B cell precursor ALL (BCP-ALL)

Strategia terapeutica basata sulla malattia residua, per una o due infusioni di cellule CARCIK-CD19 non virali modificate con sistema trasposonico. Studio di fase II in pazienti pediatrici e adulti con LLA a precursori B in recidiva o refrattaria (BCP-LLA)

A.3.1

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

Residual disease driven strategy for CARCIK (CD19) in adults/pediatric BCP-ALL

Strategia terapeutica guidata dalla malattia residua per CARCIK (CD19) in pazienti adulti/pediatrici con BCP-LLA

A.3.2

Name or abbreviated title of the trial where available

FT03CARCIK

A.4.1

Sponsor's protocol code number

FT03CARCIK

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	FONDAZIONE TETTAMANTI M.DE MARCHI ONLUS
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	AIFA - Italian Medicines Agency
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	FONDAZIONE MBBM
B.5.2	Functional name of contact point	UNITA' DI RICERCA CLINICA
B.5.3	Address:
B.5.3.1	Street Address	VIA PERGOLESI 33
B.5.3.2	Town/ city	MONZA
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	0392333525
B.5.5	Fax number	0392336827
B.5.6	E-mail	sperimentazioneclinica@fondazionembbm.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	CARCIK-CD19
D.3.2	Product code	[PTG-CARCIK-CD19]
D.3.4	Pharmaceutical form	Suspension 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.3.9.2	Current sponsor code	PTG-CARCIK-CD19
D.3.9.3	Other descriptive name	non-viral, transposon-manipulated CARCIK-CD19 cells
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10000000 to 100000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
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

Refractory or relapsed acute B-cell lymphoblastic leukemia after haematopoietic stem cell transplantation

Leucemia Linfoblastica acuta a cellule B refrattaria o recidivata dopo trapianto di cellule staminali ematopoietiche

E.1.1.1

Medical condition in easily understood language

B-cell acute lymphoblastic leukemia (ALL)

Leucemia linfoblastica acuta a cellule B refrattaria o recidivata

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Confirm the high overall response rate at day 28 after the first CARCIK-CD19 infusion,
Improve the duration of response of patients treated with CARCIK -CD19 cells

Confermare il tasso di risposta globale al giorno 28 dopo la prima infusione di CARCIK-CD19,
migliorare la durata della risposta dei pazienti trattati con cellule CARCIK -CD19.

E.2.2

Secondary objectives of the trial

1. Overall Survival (OS).
2. Safety of the second administration of CARCIK-CD19.
3. Safety of autologous CARCIK-CD19 cells.
4. Safety of cordblood CARCIK-CD19 cells

1. Sopravvivenza globale (OS);
2. Sicurezza della seconda somministrazione di CARCIK-CD19;
3. Sicurezza delle cellule CARCIK-CD19 autologhe;
4. Sicurezza delle cellule CARCIK-CD19 da sangue cordonale

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Children (1-17) and adults (18-75 years old);
2. Relapsed or refractory adult and pediatric BCP-ALL as defined for the presence of bone marrow with = 5% lymphoblasts by morphologic assessment, or if <5%, with at least 1% of molecular disease at PCR;
3. Evidence of CD19 tumor expression in bone marrow and/or peripheral blood by flow cytometry;
4. Bone marrow with = 5% lymphoblasts by morphologic assessment at screening, or if <5%, with at least 1% of molecular disease at PCR;
5. No evidence of overall aGVHD > Grade I or chronic GVHD (cGVHD) greater than mild at time of enrollment and in the previous 30 days;
6. No longer taking immunosuppressive agents for at least 30 days prior to infusion;
7. No evidence of concomitant life-threatening infectious disease;
8. Life expectancy > 60 days;
9. Lansky/Karnofsky scores > 60;
10. Absence of severe renal disease (creatinine > x 3 normal for age);
11. Absence of severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500);
12. Patient/guardian able to give informed consent.

1. Bambini (1-17) e adulti (18-75 anni);
2. B-LLA in età adulta e pediatrica recidivante o refrattaria come definita per la presenza di midollo osseo con = 5% di linfoblasti mediante valutazione morfologica, o se <5%, con almeno l'1% di malattia molecolare alla PCR;
3. Evidenza dell'espressione del tumore CD19 nel midollo osseo e/o nel sangue periferico mediante citometria a flusso;
4. Diagnosi di LLA CD19 positiva nel midollo osseo e/o nel sangue periferico e / o nei siti extramidollari con l'esclusione del Sistema Nervoso Centrale (SNC) in caso di malattia CNS-3.
5. Nessuna evidenza di aGVHD complessiva> Grado I o GVHD cronica (cGVHD) maggiore di lieve, al momento dell'arruolamento e nei 30 giorni precedenti;
6. Non assunzione di agenti immunosoppressori per almeno 30 giorni prima dell'infusione;
7. Nessuna prova di concomitante malattia infettiva pericolosa per la vita;
8. Aspettativa di vita> 60 giorni;
9. Punteggio di Lansky / Karnofsky> 60;
10. Assenza di grave malattia renale (creatinina > x 3 normale per l'età);
11. Assenza di grave malattia epatica (bilirubina diretta> 3 mg/dl o SGOT> 500);
12. Paziente/tutore in grado di dare il consenso informato.

E.4

Principal exclusion criteria

1. GVHD Grades II-IV for patients who had previously been transplanted;
2. Any cell therapy in the last 30 days;
3. Patient with concomitant life-threatening infectious disease;
4. Lansky/Karnofsky score <60;
5. Patients with hepatic or renal disease as specific above;
6. Pregnant or breast feeding females;
7. Rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
8. Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met;
9. HIV/HBV/HCV Infection: Seropositive for HIV antibody. Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HBsAG);
10. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris and cardiac arrhythmia;
11. Active Central Nervous System (CNS) involvement by malignancy, defined as CNS-3 per National Comprehensive Cancer Network (NCCN) guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible

1. GVHD di grado II-IV per pazienti precedentemente trapiantati;
2. Qualsiasi terapia cellulare nei 30 giorni precedenti;
3. Paziente con concomitante malattia infettiva pericolosa per la vita;
4. Lansky/Karnofsky <60;
5. Pazienti con malattia epatica o renale come specificato sopra;
6. Donne incinte o che allattano;
7. Malattia rapidamente progressiva che, a giudizio dello sperimentatore e dello sponsor, comprometterebbe la capacità di completare la terapia in studio;
8. I soggetti devono recuperare dagli effetti collaterali acuti della loro precedente terapia, in modo tale da soddisfare i criteri di ammissibilità;
9. Infezione da HIV / HBV / HCV: sieropositivi per gli anticorpi HIV. con test molecolare per HCV o HBV
10. Malattia non controllata, sintomatica, intercorrente, incluse ma non limitate a infezioni, insufficienza cardiaca congestizia, angina pectoris instabile e aritmia cardiaca;
11. Coinvolgimento del sistema nervoso centrale attivo (CNS) da parte di tumori maligni, definito come CNS-3 secondo le linee guida del National Comprehensive Cancer Network (NCCN). Nota: saranno eleggibili i pazienti con una storia di malattia del SNC che è stata trattata in modo efficace.

E.5 End points

E.5.1

Primary end point(s)

ORR at 28 days after the first CARCIK-CD19 administration
DOR from day 70 for patients who achieved and maintained remission after the first or the second CARCIK-CD19 administration

ORR 28 giorni dopo la (prima) somministrazione di CARCIK-CD19
DOR dal giorno 70 per i pazienti che hanno raggiunto e mantenuto la remissione dopo la prima o la seconda somministrazione di CARCIK-CD19.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month

1 mese

E.5.2

Secondary end point(s)

Overall survival (from time infusion to death)
Safety of the second administration of allogeneic CARCIK-CD19 cells
Safety of autologous CARCIK-CD19 cells
Safety of cordblood CARCIK-CD19 cells.

Sopravvivenza globale (cioè tempo dall'infusione alla morte)
Sicurezza della seconda somministrazione di cellule CARCIK-CD19 allogeniche
Sicurezza delle cellule CARCIK-CD19 autologhe
Sicurezza delle cellule CARCIK-CD19 del sangue del cordone ombelicale.

E.5.2.1

Timepoint(s) of evaluation of this end point

36 months

36 mesi

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

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)

Yes

F.1.1.4.1