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Relapsed, Diffuse Large B-cell LymphomaPhase 1NCT02658968

Study of Betalutin for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma (LYMRIT-37-05)

A Phase 1 study testing Betalutin in people with Relapsed, Diffuse Large B-cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by Nordic Nanovector at 10 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is a phase 1, dose finding, open-label study in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This is a dose escalating study to define the maximum tolerated dose (MTD) of lutetium (177Lu)-lilotomab satetraxetan (Betalutin®) in DLBCL patients who are not eligible for autologous… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Betalutin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
10 sitesin 5 countries
Study dates
2 Mar 2017to 10 Jul 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female aged ≥18 years.
  • Histologically confirmed DLBCL (WHO classification).
  • Received at least one prior line of therapy including immuno-chemotherapy.
  • In first or subsequent relapse, or refractory to the last treatment (defined as less than a complete metabolic response to the last treatment, or disease progression within 6 months from the last treatment).
  • Not suitable for, or declined/unwilling to undergo intensive therapy, including high dose chemotherapy and autologous stem cell transplantation (ASCT).
  • Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (at least one objectively bi-dimensionally measurable (nodal) lesion (>1.5 cm in its largest dimension by CT scan).
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  • Negative human anti-mouse antibody (HAMA) test.
  • Life expectancy of at least 3 months.
  • Bone marrow tumour infiltration <25% tumour cells.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Normal organ and bone marrow function defined as:
  • Absolute neutrophil count ≥1.5 x 109/L
  • Platelet count ≥150 x 109/L;
  • Haemoglobin ≥9 g/dL
  • Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome)
  • 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)
  • Adequate renal function as demonstrated by a serum creatinine ≤1.5 mg/dL or a creatinine clearance >60 mL/min
  • Normal coagulation parameters (elevated international normalized ratio (INR), prothrombin time or activated partial thromboplastin time (APTT) ≤1.3 ULN range acceptable)
  • Women of childbearing potential must:
  • Understand that the study medication may have teratogenic risk
  • Have a negative serum pregnancy test at screening and before Betalutin injection
  • Commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin two acceptable methods of birth control with a Pearl-Index ≤ 1%. 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 amenorrhoea. Apart from abstinence, acceptable methods of birth control are:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomised partner
  • Male patients must agree to use condoms during intercourse throughout study drug therapy and the following 12 months.
  • Ability to give written, informed consent prior to any study-specific screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.
  • Capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, and has signed the informed consent document.
  • A negative Hepatitis B test (HBsAg and anti-HBc) and negative HIV test during screening

Who cannot join

  • Prior hematopoietic allogenic stem cell transplantation.
  • Prior autologous stem cell transplantation.
  • Previous total body irradiation.
  • Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other investigational agent), excluding corticosteroids within 4 weeks prior to start of study treatment (i.e. rituximab) (G-CSF or GM-CSF are permitted up to 2 weeks prior to start of study treatment.)
  • Patients who are receiving any other investigational agents.
  • Patients with known or suspected central nervous system involvement of lymphoma.
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  • 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
  • Localized 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 complete remission
  • Pregnant or breastfeeding women.
  • Exposure to another CD37 targeting drug.
  • Allergy to X ray contrast agents.
  • A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any excipient used in rituximab, lilotomab or Betalutin.
  • Has received a live attenuated vaccine within 30 days prior to enrolling in the study.
  • Evidence of severe or uncontrolled systemic diseases:
  • 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
  • Pulmonary conditions e.g. unstable or uncompensated respiratory disease
  • Hepatic, renal neurological or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives
  • 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
  • History of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome
  • Cardiac conditions, including:
  • history of acute coronary syndromes (including unstable angina)
  • class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system;
  • known uncontrolled arrhythmias (except sinus arrhythmia) in the past 24 weeks.

Trial locations and contacts

10 sites in 5 countries.

10 sites in 5 countries

United States3 sites

  • Sylvester Comprehensive Cancer Centre

    Miami, Florida, 33146

  • University of California, San Diego (UCSD) - Moores Cancer Center

    San Diego, California, 92093

  • University of California, San Francisco (UCSF) - Innovation, Technology & Alliances

    San Francisco, California, 94117

Other trials in United States

Italy3 sites

  • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

    Bologna, 40138

  • Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

    Torino, 10126

  • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento

    Verona, 37134

Other trials in Italy

United Kingdom2 sites

  • University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED

  • Christie NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Germany1 site

  • Klinikum rechts der Isar der TU München

    Munich, 81675

Other trials in Germany

Spain1 site

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

About this study

Official title: A Phase 1 Dose Finding Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) in Patients With Relapsed/Refractory, Diffuse Large B-cell Lymphoma, Not Eligible for Autologous Stem Cell Transplant

This study is a phase 1, dose finding, open-label study in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This is a dose escalating study to define the maximum tolerated dose (MTD) of lutetium (177Lu)-lilotomab satetraxetan (Betalutin®) in DLBCL patients who are not eligible for autologous stem cell transplant. The study will also assess safety and tolerability, pharmacokinetics, biodistribution and efficacy.

Being tested
Betalutin
Keywords
Radioimmunotherapy, Lu-177, Phase I study, Betalutin, ARC, Antibody Radionuclide Conjugate, HH1, Rituximab, 177Lu-DOTA-HH1, Lilotomab, Lutetium (177Lu)-lilotomab satetraxetan, Additional relevant MeSH terms:, Lymphoma, Lymphoma, Non-Hodgkin, Immune System Diseases, Immunoproliferative Disorders, Diffuse Large B-Cell Lymphoma, Lymphatic Diseases, Lymphoproliferative Disorders, Neoplasms
Medical subject headings
Recurrence, Lymphoma, Large B-Cell, Diffuse, AIDS-Related Complex, Lymphoma, Lymphoma, Non-Hodgkin, Immune System Diseases, Immunoproliferative Disorders, Lymphatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BetalutinDrug

    Also called Betalutin, lutetium (177Lu)-lilotomab satetraxetan

    Dose finding study, starting on 10 MBq/kg b.w. Betalutin® (lutetium (177Lu)-lilotomab satetraxetan), single injection with lilotomab pre-dosing.

Study groups in NCT02658968
Study groupRoleWhat they receive
BetalutinExperimental10 MBq/kg b.w., in escalated doses with lilotomab pre-dosing
Receives: Drug: Betalutin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With DLTs to Determine the MTD

    To determine the MTD of Betalutin that can be administered to DBLCL patients with lilotomab. The MTD was the highest dose at which less than two out of six participants experienced a dose limiting toxicity (DLT) defined as:

    • Haematologic toxicity:
    • Grade 4 neutropenia observed for greater than 7 days' duration
    • Grade 4 thrombocytopenia observed for greater than 7 days' duration
    • Grade 3 or 4 neutropenia associated with fever (≥38.5°C) of any duration
    • Grade 3 or 4 thrombocytopenia with bleeding
    • Thrombocytopenia with any requirement for more than one platelet transfusion before recovering to Grade 1 or less
    • Grade 4 anaemia, unexplained by underlying disease
    • Non-haematologic toxicity:
    • Grade 3 nausea/vomiting/diarrhoea lasting longer than 72 hours despite maximal care or Grade 4
    • Any other Grade 3 or 4 non-haematologic toxicities
    • Any Grade 3 or 4 electrolyte abnormalities that do not resolve to Grade 1 or baseline within 24 hours

    Measured: 12 weeks

Secondary outcomes (2)

  1. The Best Overall Tumour Response

    Efficacy evaluations are measured by tumour response rates using CT and PET/CT imaging with responses classified as described in "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification" (Cheson, 2014). The Cheson criteria, 2014 are a combined score taking into consideration, positive or negative scored PET scan, the contrast enhanced CT images and bone marrow biopsies when available.

    Measured: 3 months - 2 years

  2. Dosimetry

    Dosimetry will be evaluated by the estimated absorbed radiation dose to target organs.

    Measured: 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2016 (estimated)
  2. Study start2 Mar 2017
  3. Primary completion4 Jun 2021
  4. Study completion10 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02658968
Sponsor's protocol ID
EudraCT: 2015-001933-26
Status last verified
Jan 2024
First submitted
22 Dec 2015
Last updated
16 Jan 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 23267131

  • 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. doi: 10.2174/1874471011306010004.

    PubMed 23256748

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Betalutin in people with Relapsed, Diffuse Large B-cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by Nordic Nanovector at 10 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Italy, United Kingdom, Germany, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With DLTs to Determine the MTD (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02658968, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2024.

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