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

NCT ID: NCT02658968

Last Updated: 2024-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-02
• Study Completion Date: 2021-07-10

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.

Conditions

Relapsed, Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Betalutin

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

Group Type: EXPERIMENTAL

Betalutin

Intervention Type: DRUG

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

Interventions

Betalutin

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

Intervention Type: DRUG

Other Intervention Names

Betalutin, lutetium (177Lu)-lilotomab satetraxetan

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nordic Nanovector

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy Illidge, PhD MB BS

Role: PRINCIPAL_INVESTIGATOR

University of Manchester, The Christie NHS Foundation Trust

Locations

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

San Diego, California, United States

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

San Francisco, California, United States

Sylvester Comprehensive Cancer Centre

Miami, Florida, United States

Klinikum rechts der Isar der TU München

Munich, , Germany

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

Bologna, , Italy

Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

Torino, , Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento

Verona, , Italy

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

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

Bristol, , United Kingdom

Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Germany; Italy; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 23267131 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23256748 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

EudraCT: 2015-001933-26

Identifier Type: -

Identifier Source: org_study_id