NCT02658968

Brief 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 stem cell transplant. The study will also assess safety and tolerability, pharmacokinetics, biodistribution and efficacy.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2017

Longer than P75 for phase_1

Geographic Reach
5 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 22, 2015

Completed
29 days until next milestone

First Posted

Study publicly available on registry

January 20, 2016

Completed
1.1 years until next milestone

Study Start

First participant enrolled

March 2, 2017

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 4, 2021

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 10, 2021

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

January 16, 2024

Completed
Last Updated

January 16, 2024

Status Verified

January 1, 2024

Enrollment Period

4.3 years

First QC Date

December 22, 2015

Results QC Date

May 9, 2022

Last Update Submit

January 12, 2024

Conditions

Relapsed, Diffuse Large B-cell LymphomaRefractory Diffuse Large B-Cell Lymphoma

Keywords

RadioimmunotherapyLu-177Phase I studyBetalutinARCAntibody Radionuclide ConjugateHH1Rituximab177Lu-DOTA-HH1LilotomabLutetium (177Lu)-lilotomab satetraxetanAdditional relevant MeSH terms:LymphomaLymphoma, Non-HodgkinImmune System DiseasesImmunoproliferative DisordersDiffuse Large B-Cell LymphomaLymphatic DiseasesLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic TypeDLBCLRefractory DLBCLRelapsed DLBCL

Outcome Measures

Primary Outcomes (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

    12 weeks

Secondary Outcomes (2)

  • The Best Overall Tumour Response

    3 months - 2 years

  • Dosimetry

    3 weeks

Study Arms (1)

Betalutin

EXPERIMENTAL

10 MBq/kg b.w., in escalated doses with lilotomab pre-dosing

Drug: Betalutin

Interventions

BetalutinDRUG

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

Also known as: Betalutin, lutetium (177Lu)-lilotomab satetraxetan
Betalutin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).
  • 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)
  • +17 more criteria

You may not qualify if:

  • 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.
  • 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.
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

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

San Diego, California, 92093, United States

Location

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

San Francisco, California, 94117, United States

Location

Sylvester Comprehensive Cancer Centre

Miami, Florida, 33146, United States

Location

Klinikum rechts der Isar der TU München

Munich, 81675, Germany

Location

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

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento

Verona, 37134, Italy

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

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

Bristol, BS2 8ED, United Kingdom

Location

Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 23267131BACKGROUND

  • 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.

    PMID: 23256748BACKGROUND

MeSH Terms

Conditions

RecurrenceLymphoma, Large B-Cell, DiffuseAIDS-Related ComplexLymphomaLymphoma, Non-HodgkinImmune System DiseasesImmunoproliferative DisordersLymphatic DiseasesLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic Type

Interventions

tetulomab tetraxetan lu-177Lutetium

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellHemic and Lymphatic DiseasesHIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Lanthanoid Series ElementsMetals, Rare EarthElementsInorganic ChemicalsTransition ElementsMetals

Results Point of Contact

Title
Head of Clinical Operations
Organization
Nordic Nanovector
mail@nordicnanovector.com
+47 22 18 33 01

Study Officials

  • Timothy Illidge, PhD MB BS

    University of Manchester, The Christie NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 22, 2015

First Posted

January 20, 2016

Study Start

March 2, 2017

Primary Completion

June 4, 2021

Study Completion

July 10, 2021

Last Updated

January 16, 2024

Results First Posted

January 16, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

GB(2)DE(1)US(3)ES(1)IT(3)