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

January 12, 2024 updated by: Nordic Nanovector

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, 81675
        • Klinikum rechts der Isar der TU München
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
      • Torino, Italy, 10126
        • Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino
      • Verona, Italy, 37134
        • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento
  • Spain
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
      • Manchester, United Kingdom, M20 4BX
        • Christie NHS Foundation Trust
  • United States
    • California
      • San Diego, California, United States, 92093
        • University of California, San Diego (UCSD) - Moores Cancer Center
      • San Francisco, California, United States, 94117
        • University of California, San Francisco (UCSF) - Innovation, Technology & Alliances
    • Florida
      • Miami, Florida, United States, 33146
        • Sylvester Comprehensive Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female aged ≥18 years.
  2. Histologically confirmed DLBCL (WHO classification).
  3. Received at least one prior line of therapy including immuno-chemotherapy.
  4. 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).
  5. Not suitable for, or declined/unwilling to undergo intensive therapy, including high dose chemotherapy and autologous stem cell transplantation (ASCT).
  6. 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).
  7. Negative human anti-mouse antibody (HAMA) test.
  8. Life expectancy of at least 3 months.
  9. Bone marrow tumour infiltration <25% tumour cells.
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

  11. Normal organ and bone marrow function defined as:

    1. Absolute neutrophil count ≥1.5 x 109/L
    2. Platelet count ≥150 x 109/L;
    3. Haemoglobin ≥9 g/dL
    4. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome)
    5. 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)
    6. Adequate renal function as demonstrated by a serum creatinine ≤1.5 mg/dL or a creatinine clearance >60 mL/min
    7. Normal coagulation parameters (elevated international normalized ratio (INR), prothrombin time or activated partial thromboplastin time (APTT) ≤1.3 ULN range acceptable)

  12. Women of childbearing potential must:

    1. Understand that the study medication may have teratogenic risk
    2. Have a negative serum pregnancy test at screening and before Betalutin injection

    3. 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
  13. Male patients must agree to use condoms during intercourse throughout study drug therapy and the following 12 months.
  14. 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.
  15. Capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, and has signed the informed consent document.
  16. A negative Hepatitis B test (HBsAg and anti-HBc) and negative HIV test during screening

Exclusion Criteria:

  1. Prior hematopoietic allogenic stem cell transplantation.
  2. Prior autologous stem cell transplantation.
  3. Previous total body irradiation.
  4. 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.)
  5. Patients who are receiving any other investigational agents.
  6. Patients with known or suspected central nervous system involvement of lymphoma.

  7. History of a previous treated cancer except for the following:

    1. Adequately treated local basal cell or squamous cell carcinoma of the skin
    2. Cervical carcinoma in situ
    3. Superficial bladder cancer
    4. Localized prostate cancer undergoing surveillance or surgery
    5. Localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy
    6. Other adequately treated Stage 1 or 2 cancer currently in complete remission
  8. Pregnant or breastfeeding women.
  9. Exposure to another CD37 targeting drug.
  10. Allergy to X ray contrast agents.
  11. A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any excipient used in rituximab, lilotomab or Betalutin.
  12. Has received a live attenuated vaccine within 30 days prior to enrolling in the study.

  13. Evidence of severe or uncontrolled systemic diseases:

    1. 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
    2. Pulmonary conditions e.g. unstable or uncompensated respiratory disease
    3. Hepatic, renal neurological or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives
    4. 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
    5. History of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome

    6. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Betalutin
10 MBq/kg b.w., in escalated doses with lilotomab pre-dosing
Drug: Betalutin
Dose finding study, starting on 10 MBq/kg b.w. Betalutin® (lutetium (177Lu)-lilotomab satetraxetan), single injection with lilotomab pre-dosing.
Other Names:
  • Betalutin, lutetium (177Lu)-lilotomab satetraxetan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With DLTs to Determine the MTD
Time Frame: 12 weeks

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dosimetry
Time Frame: 3 weeks
Dosimetry will be evaluated by the estimated absorbed radiation dose to target organs.
3 weeks
The Best Overall Tumour Response
Time Frame: 3 months - 2 years
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.
3 months - 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nordic Nanovector

Investigators

  • Principal Investigator: Timothy Illidge, PhD MB BS, University of Manchester, The Christie NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2017

Primary Completion (Actual)

June 4, 2021

Study Completion (Actual)

July 10, 2021

Study Registration Dates

First Submitted

December 22, 2015

First Submitted That Met QC Criteria

January 15, 2016

First Posted (Estimated)

January 20, 2016

Study Record Updates

Last Update Posted (Estimated)

January 15, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT: 2015-001933-26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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