Summary
EudraCT Number:2017-004506-18
Sponsor's Protocol Code Number:LYMRIT-37-07
National Competent Authority:Norway - NOMA
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2018-01-02
Trial results
A. Protocol Information
A.1Member State ConcernedNorway - NOMA
A.2EudraCT number2017-004506-18
A.3Full title of the trial
A phase 2 open-label study of Betalutin in combination with rituximab in patients with relapsed/refractory follicular lymphoma (Archer-1)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Treatment of lymphoma with targeted internal radiation therapy (Betalutin) in combination with rituximab
A.4.1Sponsor's protocol code numberLYMRIT-37-07
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorNordic Nanovector ASA
B.1.3.4CountryNorway
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportKreftforeningen
B.4.2CountryNorway
B.4.1Name of organisation providing supportSkattefunn
B.4.2CountryNorway
B.4.1Name of organisation providing supportInnovation Norway
B.4.2CountryNorway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationNordic Nanovector ASA
B.5.2Functional name of contact pointClinical Research Manager
B.5.3 Address:
B.5.3.1Street AddressKjelsåsveien 168B
B.5.3.2Town/ cityOslo
B.5.3.3Post codeN-0884
B.5.3.4CountryNorway
B.5.4Telephone number+4793066092
B.5.5Fax number+4722580007
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/03/14/1271
D.3 Description of the IMP
D.3.1Product nameBetalutin
D.3.2Product code Lutetium (177Lu)-lilotomab satetraxetan
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntrauterine use
Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNlutetium (177Lu)-lilotomab satetraxetan
D.3.9.1CAS number 1453362-90-7
D.3.9.2Current sponsor code177Lu-DOTA-HH1
D.3.9.3Other descriptive name177LU-TETRAXETAN-HH1
D.3.9.4EV Substance CodeSUB121341
D.3.10 Strength
D.3.10.1Concentration unit MBq/ml megabecquerel(s)/millilitre
D.3.10.2Concentration typerange
D.3.10.3Concentration number770 to 5200
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product Yes
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameLilotomab
D.3.2Product code HH1
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLilotomab
D.3.9.1CAS number 1453362-55-4
D.3.9.2Current sponsor codeHH1
D.3.9.3Other descriptive nameTETULOMAB
D.3.9.4EV Substance CodeSUB121342
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name MabThera
D.2.1.1.2Name of the Marketing Authorisation holderRoche
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/14/1271 in follicular lymphoma
D.3 Description of the IMP
D.3.1Product nameMabThera
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNRITUXIMAB
D.3.9.1CAS number 174722-31-7
D.3.9.4EV Substance CodeSUB12570MIG
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number500
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another 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.1.1Medical condition(s) being investigated
Follicular lymphoma
E.1.1.1Medical condition in easily understood language
Lymph cancer
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10029547
E.1.2Term Non-Hodgkin's lymphoma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
Primary
• To evaluate preliminary anti-tumour activity of combination treatment based on Investigator assessment of tumour response rates

E.2.2Secondary objectives of the trial
Secondary
• To evaluate the duration of tumour control in patients receiving Betalutin in combination with RTX
• To characterize the safety and tolerability of Betalutin combined with RTX
• To investigate the immunogenicity of Betalutin in combination with RTX
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Patient must be ≥ 18 years at the time of signing the informed consent
2. A pre-study ECOG performance status of 0-2
3. Histologically confirmed diagnosis (by 2008 WHO classification) of indolent non-Hodgkin B-cell follicular lymphoma (grade 1, 2 or 3a)
4. At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or in combination with chemotherapy), with documented relapsed, refractory disease (must not be anti-CD20 antibody-refractory) or PD
5. Presence of at least one bi-dimensionally measurable lesion by CT: longest diameter (LDi) >1.5 cm for a nodal lesion; LDi >1.0 cm for an extranodal lesion within 28 days prior to start of treatment
6. Normal organ and bone marrow function defined as:
a. Absolute neutrophil count ≥1.5 x 10*9/L;
b. Platelet count ≥150 x 10*9/L;
c. Haemoglobin ≥9 g/dL;
d. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert’s syndrome [< 3.0 mg/dL]);
e. Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase (ALP) ≤2.5 x ULN (or ≤ 5.0 x ULN if liver involvement by primary disease);
f. Adequate renal function as demonstrated by a serum creatinine <1.5 x ULN;
7. Bone marrow involvement by lymphoma <25%
8. Life expectancy >3 months
9. Negative hepatitis B, hepatitis C and HIV screening tests
10. Negative ADA test at screening for lilotomab/Betalutin
11. Women of childbearing potential (see Protocol Appendix 3) must:
a. have a negative serum pregnancy test at screening and before Betalutin injection
b. understand that the study medication is expected to have teratogenic risk
c. agree to use, and be able to comply with, highly effective method of birth control with a Pearl Index ≤ 1%.
Contraception is required without interruption, from 4 weeks before starting study drug, throughout study drug therapy and for 12 months after end of study drug therapy, even if she has amenorrhea
12. Male patients must agree to use condoms (See Protocol Appendix 3) during intercourse throughout study drug therapy and the following 12 months
13. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
14. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
E.4Principal exclusion criteria
1. Previous haematopoietic stem cell transplantation (autologous and allogenic)
2. Evidence of histological transformation from FL to DLBCL at time of screening.
3. Previous total body irradiation
4. Chemotherapy, immunotherapy, radioimmunotherapy, or investigational therapy within 28 days before the start of study drug treatment (corticosteroid treatment at doses of ≤ 20 mg/day, topical or inhaled corticosteroids, G-CSF or GM CSF are permitted up to 2 weeks prior to start of study treatment) or failure to recover from adverse events (AEs) associated with prior treatment
5. Patients who are receiving any other investigational medicinal products
6. Known or suspected central nervous system (CNS) involvement of lymphoma
7. History of a previous treated cancer 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. localised prostate cancer undergoing surveillance or surgery
e. localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy
f. other adequately treated Stage 1 or 2 cancer currently in CR
8. Pregnant or lactating women (See Protocol Appendix 3)
9. Exposure to another CD37 targeting drug
10. A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin
11. Receipt of live, attenuated vaccine within 30 days prior to enrolment
12. 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. Pulmonary conditions e.g. unstable or uncompensated respiratory disease
c. Hepatic, renal, neurological, or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives
d. Psychiatric conditions e.g. patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the study
e. History of erythema multiforme, toxic epidermal necrolysis, or Stevens Johnson syndrome
f. Cardiac conditions, including:
i. history of acute coronary syndromes (including unstable angina)
ii. class II, III, or IV heart failure as defined by the NYHA functional classification system
iii. known uncontrolled arrhythmias (except sinus arrhythmia) in the past 24 weeks
E.5 End points
E.5.1Primary end point(s)
• Responses [(overall response rate (ORR), CR, PR, stable disease (SD), progressive disease (PD)] as per Cheson 2014
E.5.1.1Timepoint(s) of evaluation of this end point
From baseline and up to 5 years post injection
E.5.2Secondary end point(s)
• Duration of response (DoR)
• Progression free survival (PFS)
• Time to progression (TTP)
• Overall survival (OS)
• Frequency and severity of adverse events (AEs) and laboratory abnormalities graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
• Monitoring of the anti-drug antibody (ADA) response towards lilotomab, Betalutin and/or RTX
E.5.2.1Timepoint(s) of evaluation of this end point
From baseline and up to 5 years post injection
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
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 No
E.8.4.1Number of sites anticipated in Member State concerned1
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA3
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
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.8.9.1In the Member State concerned years6
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years6
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 8
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 17
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state6
F.4.2 For a multinational trial
F.4.2.1In the EEA 25
F.4.2.2In the whole clinical trial 25
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)
The patient will follow routinely control as requested by treating physician
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2018-02-26
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2018-06-13
P. End of Trial
P.End of Trial StatusOngoing