Clinical Trials Register

Summary
EudraCT Number:	2015-001570-17
Sponsor's Protocol Code Number:	LYMRIT-37-06
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-07-07
Trial results	View 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2015-001570-17

A.3

Full title of the trial

A Phase 2 study of the antibody-radionuclide-conjugate 177Lu-DOTA-HH1 (Betalutin™) in patients with CD37-positive relapsed follicular lymphoma

A.3.1

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

A study to identify the most effective dose of Betalutin in patients with a type of follicular lymphoma that is CD37-positive which has recurred

A.4.1

Sponsor's protocol code number

LYMRIT-37-06

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	Nordic Nanovector ASA
B.1.3.4	Country	Norway
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	Nordic Nanovector ASA
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Nordic Nanovector ASA
B.5.2	Functional name of contact point	Clinical Trials Department
B.5.3	Address:
B.5.3.1	Street Address	Kjelsåsveien 168B
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	N-0884
B.5.3.4	Country	Norway
B.5.6	E-mail	mail@nordicnanovector.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1271
D.3 Description of the IMP
D.3.1	Product name	Betalutin
D.3.2	Product code	177Lu-DOTA-HH1
D.3.4	Pharmaceutical form	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	-
D.3.9.1	CAS number	1453362-90-7
D.3.9.2	Current sponsor code	177Lu-DOTA-HH1
D.3.9.3	Other descriptive name	177Lu-tetraxetan-teleulomab
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	8 to 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	Yes
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	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.2.5	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.3.2	Product code	Rituximab
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.3.11 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.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	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	Tetulomab
D.3.2	Product code	HH1
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	-
D.3.9.1	CAS number	1453362-55-4
D.3.9.2	Current sponsor code	HH1
D.3.9.3	Other descriptive name	TETULOMAB
D.3.9.4	EV Substance Code	SUB121342
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	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	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 CD37+ non-Hodgkin B-cell follicular lymphoma

E.1.1.1

Medical condition in easily understood language

Cancer of the white blood cells

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10029547
E.1.2	Term	Non-Hodgkin's lymphoma
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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10003902
E.1.2	Term	B-cell lymphoma recurrent
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

● Part 1: To identify the optimal dose of Betalutin in terms of overall response rate (ORR), assessed with the use of standard criteria for Lymphoma.

● Part 2: To assess the ORR assessed with the use of standard criteria for Lymphoma

E.2.2

Secondary objectives of the trial

● To assess the best overall response rate
● To assess the duration of response
● To estimate progression free survival (PFS)
● To assess the time to next treatment
● To estimate overall survival (OS)
● To investigate Quality of Life (QoL)
● To investigate safety and toxicity of Betalutin

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically confirmed (by World Health Organization [WHO] classification) follicular lymphoma (follicular grade I-IIIA)

2. Relapsed after 2 or more prior systemic regimens

3. Requiring initiation of treatment for the NHL

4. Age ≥18 years

5. ECOG performance status of 0-2

6. Life expectancy of at least 3 months

7. Bone marrow tumour infiltration <25% tumour cells

8. CD37-positive; re-biopsy or test existing tumour material if not known

9. Negative HAMA test

10. Laboratory values within 15 days before study enrolment:
a) Absolute Neutrophil Counts ≥ 1.5 x 109/l
b) Platelet count ≥ 150 x 109 /l
c) Total bilirubin ≤ 1.5 x upper limit of normal
d) Alkaline Phosphatase ≤ 4x normal level
e) ALAT ≤ 4x normal level
f) Creatinine ≤110 μmol/L (men), 90 μmol/L (women)

11. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (according to standard criteria: at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan).

12. Women of childbearing potential must:
a. understand that the study medication is expected to have teratogenic risk
b. have a negative serum pregnancy test at screening and before Betalutin injection
c. commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control with a Pearl-Index ≤ 1%. without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 5 months after end of study drug therapy, even if she has amenorrhoea

13. Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 5 months

14. The patient has been fully informed about the study and has signed the informed consent form

15. The patient is willing and able to comply with the protocol and agrees to return to the hospital for follow-up visits and examination

E.4

Principal exclusion criteria

1. Evidence of severe or uncontrolled systemic diseases:
a) Uncontrolled infection including evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
b) Known to be HIV positive
c) Pulmonary conditions e.g. unstable or uncompensated respiratoryd) Hepatic conditions
e) Renal conditions
f) Neurological conditions
g) Psychiatric conditions
h) Metabolic conditions
i) History of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome
j) Cardiac conditions, including
i. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks
ii. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
iii. Known uncontrolled arrhythmias (except sinus arrhythmia) in the past 24 weeks.

2. Bulky disease defined as the presence of one or more nodes with at least one dimension of 10 cm or more.

3. Ongoing immunosuppressive therapy, including systemic corticosteroids. Patients may be using topical or inhaled corticosteroids

4. Known or suspected central nervous system involvement of lymphoma

5. Previous total body irradiation, or irradiation of >25% of the patient’s bone marrow

6. Investigational drug, chemotherapy, or immunotherapy received within the last 4 weeks prior to start of study treatment, except for the pre-treatment used in this study

7. Pregnant or lactating women

8. Prior hematopoietic allogenic stem cell transplantation

9. Prior autologous stem cell transplantation ≤2 years ago

10. History of a non-lymphoma malignancy except for the following:
a) adequately treated local basal cell or squamous cell carcinoma of the skin
b) cervical carcinoma in situ
c) superficial bladder cancer
d) localized prostate cancer
e) other adequately treated Stage 1 or 2 cancer currently in complete remission
f) or any other cancer that has been in complete remission for ≥ 5 years

11. Allergy to X ray contrast agents

E.5 End points

E.5.1

Primary end point(s)

Overall response rate (ORR), defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) assessed with the use of standard criteria for lymphoma; in part 2 of the study, responses will be assessed by the independent image review committee. ORR scored at 3 months will be used for primary efficacy end-point.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 3 months

E.5.2

Secondary end point(s)

1) Best overall response rate

2) Duration of tumour response (DOR)

3) PFS (Performance Status)

4) Time to next treatment

5) OS (Overall Survival)

E.5.2.1

Timepoint(s) of evaluation of this end point

1) 5 years

2) Time from the date of the onset of response to the first documentation of relapse or progressive disease, whichever occurs first.

3) Defined as the interval from Betalutin administration and date of: relapse (new or enlarged lesions after CR); progression (new or enlarged lesions after PR or stable disease [SD]), or death from any cause. If none of the above events are observed, PFS should be censored at the date of the last assessment (i.e. last CT scan). Cheson criteria is used for definition of new or enlarged lesion.

4) The time from Betalutin administration to the start of the next anti-cancer therapy.

5) From the date of study entry until the date of death of any cause.

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Canada

Czech Republic

Denmark

France

Germany

Hungary

Israel

Italy

Netherlands

Norway

Poland

Russian Federation

Spain

Sweden

Turkey

United Kingdom

United States

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

LSLV

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

125

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)

Standard of care

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

2015-09-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-08-07

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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