<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03806179</url>
  </required_header>
  <id_info>
    <org_study_id>LYMRIT -37-07(Archer-1)</org_study_id>
    <secondary_id>2017-004506-18</secondary_id>
    <nct_id>NCT03806179</nct_id>
  </id_info>
  <brief_title>Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL</brief_title>
  <acronym>LYMRIT-37-07</acronym>
  <official_title>A Phase 1b Open-label Study of Betalutin in Combination With Rituximab in Patients With Relapsed/Refractory Follicular Lymphoma (Archer-1)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordic Nanovector</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ICON Clinical Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nordic Nanovector</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a Phase 1b, open-label, single arm dose escalation study of Betalutin followed&#xD;
      by rituximab in patients with previously treated follicular lymphoma. The purpose of this&#xD;
      study is to characterise the safety, tolerability, pharmacokinetics, pharmacodynamics and&#xD;
      preliminary anti-tumour activity of Betalutin in combination with rituximab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 4, 2018</start_date>
  <completion_date type="Actual">August 8, 2022</completion_date>
  <primary_completion_date type="Actual">August 8, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability: frequency and severity of adverse events (CTCAE v4.03)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preliminary Anti-tumour Activity</measure>
    <time_frame>25 months</time_frame>
    <description>Preliminary anti-tumour activity of combination treatment based on tumour response rates per Cheson 2014</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Non Hodgkin Lymphoma</condition>
  <condition>Follicular Lymphoma</condition>
  <condition>Relapsed Follicular Lymphoma</condition>
  <arm_group>
    <arm_group_label>Betalutin with rituximab treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Betalutin</intervention_name>
    <description>Betalutin 10, 15 MBq/kg; lilotomab 40mg, rituximab 375 mg/m2</description>
    <arm_group_label>Betalutin with rituximab treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must be ≥18 years at the time of signing the informed consent&#xD;
&#xD;
          -  ECOG performance status of 0-2&#xD;
&#xD;
          -  Histologically confirmed diagnosis (by 2008 World Health Organization [WHO]&#xD;
             classification) of follicular lymphoma (grade 1, 2 or 3a)&#xD;
&#xD;
          -  At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or&#xD;
             in combination with chemotherapy), with documented relapsed, refractory disease (must&#xD;
             not be anti-CD20 antibody-refractory) or PD&#xD;
&#xD;
          -  Presence of at least one bi-dimensionally measurable lesion by CT or MRI: longest&#xD;
             diameter (LDi) &gt;1.5 cm for a nodal lesion; LDi &gt;1.0 cm for an extranodal lesion within&#xD;
             28 days prior to start of treatment&#xD;
&#xD;
          -  Normal organ and bone marrow function defined as:&#xD;
&#xD;
               1. Absolute neutrophil count ≥1.5 x 109/L;&#xD;
&#xD;
               2. Platelet count ≥150 x 109/L;&#xD;
&#xD;
               3. Haemoglobin ≥9 g/dL;&#xD;
&#xD;
               4. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with&#xD;
                  documented Gilbert's syndrome [&lt;3.0 mg/dL]);&#xD;
&#xD;
               5. Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase&#xD;
                  (ALP) ≤2.5 x ULN (or ≤5.0 x ULN if liver involvement by primary disease);&#xD;
&#xD;
               6. Adequate renal function as demonstrated by a serum creatinine within the upper&#xD;
                  limit of normal range&#xD;
&#xD;
          -  Bone marrow involvement by lymphoma &lt;25%&#xD;
&#xD;
          -  Life expectancy &gt;3 months&#xD;
&#xD;
          -  Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening&#xD;
             tests&#xD;
&#xD;
          -  Patients must agree to use effective contraception for 12 months following last study&#xD;
             drug administration&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Previous haematopoietic stem cell transplantation (autologous and allogenic)&#xD;
&#xD;
          -  Evidence of histological transformation from FL to DLBCL at time of screening.&#xD;
&#xD;
          -  Previous total body irradiation&#xD;
&#xD;
          -  Chemotherapy, immunotherapy or investigational therapy within 28 days before the start&#xD;
             of study drug administration (corticosteroid treatment at doses of ≤20 mg/day, topical&#xD;
             or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or&#xD;
             granulocyte-macrophage colony-stimulating factor [GM CSF] are permitted up to 2 weeks&#xD;
             prior to start of study treatment) or failure to recover from AEs associated with&#xD;
             prior treatment&#xD;
&#xD;
          -  Previous treatment with radioimmunotherapy&#xD;
&#xD;
          -  Patients who are receiving any other investigational medicinal products&#xD;
&#xD;
          -  Known or suspected central nervous system (CNS) involvement of lymphoma&#xD;
&#xD;
          -  History of a previous treated cancer except for the following:&#xD;
&#xD;
               1. adequately treated local basal cell or squamous cell carcinoma of the skin&#xD;
&#xD;
               2. cervical carcinoma in situ&#xD;
&#xD;
               3. superficial bladder cancer or localised prostate cancer undergoing surveillance&#xD;
                  or surgery&#xD;
&#xD;
               4. localised breast cancer treated with surgery and radiotherapy but not including&#xD;
                  systemic chemotherapy&#xD;
&#xD;
               5. other adequately treated Stage 1 or 2 cancer currently in CR&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Exposure to another CD37 targeting drug&#xD;
&#xD;
          -  A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any&#xD;
             excipient used in RTX, lilotomab or Betalutin&#xD;
&#xD;
          -  Receipt of live, attenuated vaccine within 30 days prior to enrolment&#xD;
&#xD;
          -  Evidence of severe or uncontrolled systemic diseases (e.g. ongoing infection,&#xD;
             respiratory, cardiac, hepatic or psychiatric conditions) which in the Investigator's&#xD;
             opinion would compromise the protocol objectives&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexander Fosså, MD.PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oslo University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinika Hematoonkologie</name>
      <address>
        <city>Ostrava-</city>
        <state>Porubá</state>
        <zip>807-52</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>N-0310</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Norway</country>
  </location_countries>
  <removed_countries>
    <country>Poland</country>
    <country>United Kingdom</country>
  </removed_countries>
  <link>
    <url>http://www.nordicnanovector.com</url>
    <description>Sponsor home page</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>29993152</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>September 30, 2022</last_update_submitted>
  <last_update_submitted_qc>September 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Radioimmunotherapy</keyword>
  <keyword>Lu-177</keyword>
  <keyword>Betalutin</keyword>
  <keyword>Phase 1b</keyword>
  <keyword>Combination</keyword>
  <keyword>Rituximab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>January 15, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03806179
org study id: LYMRIT -37-07(Archer-1)
secondary id: 2017-004506-18
nct id: NCT03806179
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and Tolerability: frequency and severity of adverse events (CTCAE v4.03)
time frame: 12 weeks
description: Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03)
measure: Preliminary Anti-tumour Activity
time frame: 25 months
description: Preliminary anti-tumour activity of combination treatment based on tumour response rates per Cheson 2014
arm group label: Betalutin with rituximab treatment
arm group type: Experimental
description: 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
intervention type: Drug
intervention name: Betalutin
description: Betalutin 10, 15 MBq/kg; lilotomab 40mg, rituximab 375 mg/m2
arm group label: Betalutin with rituximab treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexander Fosså, MD.PhD
role: Principal Investigator
affiliation: Oslo University Hospital
facility: 
facility: 
country: Czechia
country: Norway
country: Poland
country: United Kingdom
url: http://www.nordicnanovector.com
description: Sponsor home page
citation: 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
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
sharing ipd: No
submitted: January 15, 2023