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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01796171




Registration number
NCT01796171
Ethics application status
Date submitted
19/02/2013
Date registered
21/02/2013
Date last updated
13/05/2020

Titles & IDs
Public title
A Phase I/II Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma
Scientific title
A Phase I/II Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.
Secondary ID [1] 0 0
EudraCT: 2011-000033-36
Universal Trial Number (UTN)
Trial acronym
LYMRIT-37-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin Lymphoma 0 0
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Betalutin
Treatment: Drugs - Betalutin
Treatment: Drugs - Betalutin
Treatment: Drugs - Betalutin
Treatment: Drugs - Betalutin
Treatment: Drugs - Betalutin

Experimental: Part A, Arm 1: with lilotomab pre-dosing - Betalutin, 10 MBq/kg b.w. in escalated doses with lilotomab pre-dosing.

Experimental: Part A, Arm 2: without pre-dosing - Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing.

Experimental: Part A, Arm 3: with rituximab pre-dosing - Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing.

Experimental: Part A, Arm 4: with higher dose lilotomab pre-dosing - Betalutin, 15 MBq/kg b.w. in escalated doses with a higher dose lilotomab pre-dosing regimen.

Experimental: Part A, Arm 5: with intermediate dose lilotomab pre-dosing - Betalutin, 20 MBq/kg b.w. with an intermediate dose lilotomab pre-dosing regimen.

Experimental: Part B - Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20 MBq/kg b.w. with 100mg/m2 lilotomab


Treatment: Drugs: Betalutin
Betalutin, 10 MBq/kg b.w. in escalated doses with 40 mg lilotomab pre-dosing

Treatment: Drugs: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing

Treatment: Drugs: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing

Treatment: Drugs: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses with 100 mg/m2 lilotomab pre-dosing

Treatment: Drugs: Betalutin
Betalutin, 20 MBq/kg b.w. in escalated doses with 60 mg/m2 lilotomab pre-dosing

Treatment: Drugs: Betalutin
Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20 MBq/kg b.w. with 100 mg/m2 lilotomab

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A, Phase I - To define Maximum tolerated dose (MTD) of Betalutin Adverse events and abnormal laboratory values will be graded for toxicity according to CTCAE version 4.
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Part A, Phase IIa - To explore tumour response rates in patients receiving Betalutin
Timepoint [2] 0 0
3 months - 5 years
Primary outcome [3] 0 0
Part B, Phase IIb - Overall response rate
Timepoint [3] 0 0
3 months - 5 years

Eligibility
Key inclusion criteria
Part A:



- Histologically confirmed (by WHO classification) relapsed incurable non-Hodgkin B-cell
lymphoma of following subtypes; follicular grade I-IIIA, marginal zone, small
lymphocytic, lymphoplasmacytic, mantle cell.

- Age = 18 years

- A pre-study WHO performance status of 0-1

- Life expectancy should be = 3 months

- <25% tumour cells in bone marrow biopsy

- Measurable disease by radiological methods
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Absolute Neutrophil Counts (ANC) = 1.5 x 109 /l

- Platelet count = 150 x 109 /l

- Total bilirubin = 30 mmol/l

- ALP and ALAT = 4x normal level

- Creatinine = 115 µmol/l (men), 97 µmol/l (women))

- Known CNS involvement of lymphoma

- Previous total body irradiation

- Known history of HAMA

- Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study
treatment. Pretreatment with rituximab is allowed

- Previous hematopoietic stem cell transplantation (autologous and allogenic)

- Previous treatment with radioimmunotherapy

- Receipt of live, attenuated vaccine within 30 days prior to enrolment

- Test positive for hepatitis B (HBsAg and anti-HBc)

- A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any
excipient used in rituximab, HH1 or Betalutin

Part B:

Inclusion Criteria:

- Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL
(follicular grade I-IIIA).

- Male or female aged = 18 years.

- Received at least 2 prior chemotherapy- or immunotherapy-based regimens. Prior therapy
must include a rituximab/anti-CD20 agent and alkylating agent. Prior exposure to other
systemic anti-neoplastic agents (including idelalisib or other PI3K inhibitors) is
also allowed.

- Patients must be refractory to any previous regimen containing rituximab/anti-CD20
agent, defined as no response (no CR or PR) during therapy or a response (CR/PR)
lasting less than 6 months after the completion of a regimen of rituximab/anti-CD20
therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20
maintenance therapy, or within 6 months of completion of maintenance therapy).

- WHO performance status of 0-2.

- Life expectancy of = 3 months.

- Bone marrow tumour infiltration < 25% (in biopsy taken from a site not previously
irradiated).

- Measurable disease by CT or MRI: longest diameter (LDi) > 1.5 cm for nodal lesion, LDi
> cm for extra nodal lesion within 28 days prior to start of treatment.

- ANC = 1.5 x 109/L.

- Platelet count = 150 x 109/L.

- Haemoglobin = 9.0 g/dL.

- Total bilirubin = 1.5 x upper limit of normal (ULN) (except patients with documented
Gilbert's syndrome [< 3.0 mg/dL]).

- Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or ALP = 2.5 x
ULN (or = 5.0 x ULN with liver involvement by primary disease).

- Adequate renal function as demonstrated by a serum creatinine < 1.5 x ULN.

- Negative HAMA test at screening.

- Negative test at screening for Hepatitis B (negative HBsAG and anti-HBC), Hepatitis C
and HIV.



- Prior hematopoietic allogenic stem cell transplantation.

- Prior autologous stem cell transplantation.

- Evidence of histological transformation from FL to DLBCL at time of screening.

- Previous total body irradiation.

- Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other investigational
agent) within 4 weeks prior to start of study 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). Note: excludes
pre-treatment with rituximab as part of this study.

- Patients with known or suspected CNS involvement of lymphoma.

- History of a previous treated cancer except for the following: adequately treated
local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,
superficial bladder cancer, localised prostate cancer undergoing surveillance or
surgery, localised breast cancer treated with surgery and radiotherapy but not
including systemic chemotherapy, other adequately treated Stage 1 or 2 cancer
currently in CR.

- Exposure to another CD37 targeting drug.

- A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any
excipient used in rituximab, lilotomab, or Betalutin.

- Has received a live-attenuated vaccine within 30 days prior to enrolment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment outside Australia
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United States of America
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Arkansas
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Kentucky
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Louisiana
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New York
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North Carolina
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Oregon
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Pennsylvania
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Texas
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Innsbruck
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Wien
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Gent
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Leuven
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Canada
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Sault Ste Marie
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Toronto
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Croatia
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Zagreb
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Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
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Aarhus
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Grenoble
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France
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Pierre-Bénite
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France
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Tours
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Hungary
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Budapest
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Ireland
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Dublin
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Ireland
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Galway
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Israel
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Afula
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Israel
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Be'er Ya'aqov
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Israel
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Israel
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Israel
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Alessandria
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Bologna
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Firenze
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Italy
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Meldola
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Milano
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Reggio Emilia
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Torino
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Korea, Republic of
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Jeonju
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Groningen
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Bergen
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Oslo
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Trondheim
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Gdynia
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Barcelona
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Cadiz
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Majadahonda
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Ourense
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Pamplona
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Salamanca
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Seville
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Valencia
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Umeå
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Switzerland
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Chur
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Adana
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Samsun
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Manchester
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Plymouth
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nordic Nanovector
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is a phase I/II, open-label study in patients with relapsed indolent non-Hodgkin
lymphoma. Part A of the study included a phase I dose escalation to define the maximum
tolerated / recommended dose for expansion of (177Lu)-lilotomab (Betalutin), and a phase IIa
part to evaluate safety and preliminary efficacy. Part B of the study will assess the
efficacy and safety of two different Betalutin/lilotomab dosing regimens in adult patients
with relapsed rituximab / anti-CD20-refractory follicular lymphoma who have received 2 or
more prior therapies.
Trial website
https://clinicaltrials.gov/show/NCT01796171
Trial related presentations / publications
Dahle J, Repetto-Llamazares AH, Mollatt CS, Melhus KB, Bruland OS, Kolstad A, Larsen RH. Evaluating antigen targeting and anti-tumor activity of a new anti-CD37 radioimmunoconjugate against non-Hodgkin's lymphoma. Anticancer Res. 2013 Jan;33(1):85-95.
Repetto-Llamazares AH, Larsen RH, Mollatt C, Lassmann M, Dahle J. Biodistribution and dosimetry of (177)Lu-tetulomab, a new radioimmunoconjugate for treatment of non-Hodgkin lymphoma. Curr Radiopharm. 2013 Mar;6(1):20-7.
Public notes

Contacts
Principal investigator
Name 0 0
Arne Kolstad, MD, PhD
Address 0 0
Oslo University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
clinicaltrials@nordicnanovector.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01796171