Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL

NCT03806179 | Completed Phase 1 Results

• 2 other identifiers: LYMRIT -37-07(Archer-1)2017-004506-18
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is a Phase 1b, open-label, single arm dose escalation study of Betalutin followed by rituximab in patients with previously treated follicular lymphoma. The purpose of this study is to characterise the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of Betalutin in combination with rituximab.

Conditions

Non Hodgkin Lymphoma; Follicular Lymphoma; Relapsed Follicular Lymphoma

Keywords

Radioimmunotherapy; Lu-177; Betalutin; Phase 1b; Combination; Rituximab

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03)

  Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin

  12 weeks

Secondary Outcomes (1)

• Preliminary Anti-tumour Activity

  25 months

Study Arms (2)

10 MBq/kg Betalutin with rituximab treatment

EXPERIMENTAL

10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years

Drug: 10 MBq/kg Betalutin

15 MBq/kg Betalutin with rituximab treatment

EXPERIMENTAL

15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years

Drug: 15 MBq/kg Betalutin

Interventions

10 MBq/kg Betalutin DRUG

10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2

10 MBq/kg Betalutin with rituximab treatment

15 MBq/kg Betalutin DRUG

15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2

15 MBq/kg Betalutin with rituximab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be ≥18 years at the time of signing the informed consent
• ECOG performance status of 0-2
• Histologically confirmed diagnosis (by 2008 World Health Organization \[WHO\] classification) of follicular lymphoma (grade 1, 2 or 3a)
• 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
• Presence of at least one bi-dimensionally measurable lesion by CT or MRI: 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
• 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 \[\<3.0 mg/dL\]);
• 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 within the upper limit of normal range
• Bone marrow involvement by lymphoma \<25%
• Life expectancy \>3 months
• Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening tests

You may not qualify if:

• Previous haematopoietic stem cell transplantation (autologous and allogenic)
• Evidence of histological transformation from FL to DLBCL at time of screening.
• Previous total body irradiation
• Chemotherapy, immunotherapy or investigational therapy within 28 days before the start of study drug administration (corticosteroid treatment at doses of ≤20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor \[GM CSF\] are permitted up to 2 weeks prior to start of study treatment) or failure to recover from AEs associated with prior treatment
• Previous treatment with radioimmunotherapy
• Patients who are receiving any other investigational medicinal products
• Known or suspected central nervous system (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 or 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
• Pregnant or lactating women
• Exposure to another CD37 targeting drug

Sponsors & Collaborators

• Nordic Nanovector: lead
• ICON Clinical Research: collaborator

Study Sites (2)

Klinika Hematoonkologie

Ostrava, Porubá, 807-52, Czechia

Location

Oslo University Hospital

Oslo, N-0310, Norway

Location

Related Publications (2)

• Repetto-Llamazares AHV, Malenge MM, O'Shea A, Eiriksdottir B, Stokke T, Larsen RH, Dahle J. Combination of 177 Lu-lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non-Hodgkin's lymphoma. Eur J Haematol. 2018 Oct;101(4):522-531. doi: 10.1111/ejh.13139. Epub 2018 Aug 31.

  PMID: 29993152 BACKGROUND

• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.

  PMID: 25113753 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Whilst the protocol makes reference to a separate statistical analysis plan, given that only seven participants were enrolled and the originally planned expansion phase in a further 20-25 participants was not performed (removed under protocol Version 4.0) a separate detailed statistical analysis plan was not generated.

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Nordic Nanovector

mail@nordicnanovector.com

+47 22 18 33 01

Study Officials

• Alexander Fosså, MD.PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 16, 2019
• Study Start: October 4, 2018
• Primary Completion: August 8, 2022
• Study Completion: August 8, 2022
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); NO (1)