Clinical Trials Register

Summary
EudraCT Number:	2014-001949-25
Sponsor's Protocol Code Number:	PH-L19IL2RTX-01/14
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-07-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2014-001949-25

A.3

Full title of the trial

A Phase I/II study of the tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein in combination with Rituximab in relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL)

A.3.1

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

Study of Phase I/II of the combination of L19IL2 with Rituximab in Diffuse Large B-cell Lymphoma

A.4.1

Sponsor's protocol code number

PH-L19IL2RTX-01/14

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	Philogen S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Philogen S.p.A.
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	Philogen S.p.A,
B.5.2	Functional name of contact point	NA
B.5.3	Address:
B.5.3.1	Street Address	Bellaria 35
B.5.3.2	Town/ city	Sovicille
B.5.3.3	Post code	53018
B.5.3.4	Country	Italy
B.5.4	Telephone number	39057717816
B.5.5	Fax number	3905771781690
B.5.6	E-mail	regulatory@philogen.com

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	Darleukin
D.3.2	Product code	L19IL2
D.3.4	Pharmaceutical form	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	Darleukin
D.3.9.2	Current sponsor code	L19IL2
D.3.9.3	Other descriptive name	L19 antibody fused to IL2
D.3.9.4	EV Substance Code	SUB27376
D.3.10	Strength
D.3.10.1	Concentration unit	million IU million international units
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	13
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	No
D.3.11.3.2	Gene therapy medical product	No
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	monoclonal recombinant antibody in scFv format linked to interleukin 2 (IL2)
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	MabThera 100 mg concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
D.3.9.2	Current sponsor code	Rituximab
D.3.9.3	Other descriptive name	Rituximab
D.3.9.4	EV Substance Code	SUB12570MIG
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	10
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	No
D.3.11.3.2	Gene therapy medical product	No
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	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

Relapsed or refractory CD20+ diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for autologous stem cell transplantation or who relapse/progress after transplantation.

E.1.1.1

Medical condition in easily understood language

Patients of large B-cell lymphoma which conditions are worsening and cannot undergo autologous stem cell transplantation or who relapse or progress after transplantation

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10012907
E.1.2	Term	Diffuse mixed small and large cell lymphoma (Diffuse large B-cell lymphoma) recurrent
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10012908
E.1.2	Term	Diffuse mixed small and large cell lymphoma (Diffuse large B-cell lymphoma) refractory
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I: 1) To assess the MTD and monitor the safety of L19IL2 in combination with Rituximab in patients with relapsed or refractory DLBCL and to describe DLT. 2) To define the RD of L19IL2 to be used in phase II when administered in combination with Rituximab to patients with relapsed or refractory DLBCL.

Phase II: To assess the therapeutic efficacy measured as complete remission rate and ORR of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL.

E.2.2

Secondary objectives of the trial

Phase I: 1)To assess objective responses of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. 2) To assess PFS and OS in patients treated within this protocol.

Phase II: To assess safety of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. To assess PFS and OS in patients treated within this protocol.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Histologically confirmed CD 20-positive DLBCL
2.Patients must have experienced relapse after or did not achieve CR with standard R-CHOP-like treatment and must be ineligible for autologous stem cell transplantation or must have relapsed/progressed after autologous or allogeneic stem cell transplantation
3.Presence of measurable lesions according to Revised response criteria for malignant lymphoma
4.Males or females, age ≥ 18 years
5.ECOG performance status ≤ 2
6.Life expectancy of at least 12 weeks
7.Absolute neutrophil count > 1.5 x 10^9/L
8.Hemoglobin > 8.0 g/dL
9.Platelets > 50 x 10^9/L
10.Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)
11.No abnormal electrocardiogram findings requiring treatment
12.ALT and AST ≤ 3.0 x the upper limit of normal (ULN) (5.0 x ULN for patients with hepatic involvement with tumor)
13.Serum creatinine < 2 x ULN
14.All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above
15.Negative serum pregnancy test (for women of child-bearing potential only) at screening
16.If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug
17.Able to provide written Informed Consent
18.Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures

E.4

Principal exclusion criteria

1.Primary central nervous system lymphoma
2.Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry
3.History of HIV infection or infectious hepatitis B or C
4.Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study
5.History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris
6.Inadequately controlled cardiac arrhythmias including atrial fibrillation
7.Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)
8.Uncontrolled hypertension
9.Ischemic peripheral vascular disease (Grade IIb-IV)
10.Severe diabetic retinopathy
11.Active autoimmune disease
12.History of organ allograft or stem cell transplantation
13.Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment
14.Known history of allergy to IL2 or other human proteins/peptides/antibodies
15.Positive serum pregnancy test (for women of child-bearing potential only) at screening
16.Breast feeding female
17.Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery)
18.Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion
19.Any conditions that in the opinion of the investigator could hamper compliance with the study protocol

E.5 End points

E.5.1

Primary end point(s)

CR Rate
ORR

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6

E.5.2

Secondary end point(s)

CR Rate
ORR

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 6

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Study of the formation of antibodies against anti- fusion protein L19IL2 (HAFA)

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.8.3

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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)

None

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

2015-01-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-09-29

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials