Dosimetry Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma (LYMRIT-37-02)

NCT02657447 | Withdrawn Phase 1

• 1 other identifier: EudraCT: 2013-003908-39
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase I, open label, randomized study to assess pharmacokinetics, biodistribution and radiation dosimetry of lutetium (177Lu) lilotomab satetraxetan (Betalutin®) radioimmunotherapy in patients with relapsed non-Hodgkin lymphoma. The study will also investigate the safety, toxicity and efficacy of Betalutin and pre-dosing.

Conditions

Non-Hodgkin Lymphoma

Keywords

Radioimmunotherapy; Lu-177; Phase I study; Betalutin; ARC; Antibody Radionuclide Conjugate; HH1; Rituximab; 177Lu-DOTA-HH1; Lymphoma; Lymphoma Non-Hodgkin; Immune System Diseases; Follicular Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytoid; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Neoplasms by Histological Type; Small Lymphocytic Lymphoma; Classical Mantle Cell Lymphoma; Lilotomab; Lutetium (177Lu) lilotomab satetraxetan

Outcome Measures

Primary Outcomes (1)

• Dosimetry

  Estimation of individual tumour/organ uptake and retention of radioactivity.

  3 weeks

Secondary Outcomes (3)

• The number of participants with adverse events as assessed by NCTCAE.

  12 weeks

• Efficacy (Best overall response rate)

  3 months - 1 year

• Lilotomab pharmacokinetics

  3 weeks

Study Arms (2)

Arm 1: Betalutin with lilotomab dose 1

EXPERIMENTAL

Betalutin 15 MBq/kg b.w. with lilotomab pre-dosing

Drug: Betalutin with lilotomab dose 1

Arm 2: Betalutin with lilotomab dose 2

EXPERIMENTAL

Betalutin 15MBq/kg b.w. with lilotomab pre-dosing

Drug: Betalutin with lilotomab dose 2

Interventions

Betalutin with lilotomab dose 1 DRUG

15 MBq/kg b.w. Betalutin (lutetium (177Lu) lilotomab satetraxetan) single injection, with lilotomab pre-dosing, dose 1

Also known as: Betalutin, Lymrit 37-02, lutetium (177Lu) lilotomab satetraxetan, HH1, 177Lu-DOTA-HH1

Arm 1: Betalutin with lilotomab dose 1

Betalutin with lilotomab dose 2 DRUG

15 MBq/kg b.w. Betalutin (lutetium (177Lu) lilotomab satetraxetan) single injection, with lilotomab pre-dosing, dose 2

Also known as: Betalutin, Lymrit 37-02, lutetium (177Lu) lilotomab satetraxetan, HH1, 177Lu-DOTA-HH1

Arm 2: Betalutin with lilotomab dose 2

Eligibility Criteria

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

You may qualify if:

• Requiring initiation of treatment for the NHL.
• Relapsed after at least one line of therapy including rituximab combination chemotherapy regimen.
• Exhausted and/or ineligible for all standard treatment options.
• Not a candidate for an autologous or allogeneic stem cell transplantation. Patients in progression after successful stem cell collection before before high-dose therapy and autologous stem cell transplantation may be considered for enrolment.
• Age ≥ 18 years..
• A pre-study ECOG performance status of 0-2. In selected patients an ECOG score of 3 can be acceptable if it is clearly lymphoma-associated at the discretion of the investigator.
• Life expectancy should be ≥ 3 months.
• \. \< 25% tumour cells in bone marrow biopsy prior to lilotomab/Betalutin treatment (biopsy taken from a site not previously irradiated).
• All patients must have at least one bi-dimensionally measurable lesion (\>1.5 cm in its largest dimension by CT scan). Patients without such a target lesion can be accepted on an individual basis if histological organ involvement can be evaluated for response e.g. involvement of the skin or the gastrointestinal tract.
• Women of childbearing potential must:
• have a negative serum pregnancy test at screening and before Betalutin injection
• understand that the study medication is expected to have teratogenic risk
• agree to use, and be able to comply with, highly effective method of birth control with a Pearl-Index ≤ 1%. Contraception is required without interruption, 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.
• Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 12 months.
• Patients previously treated with native rituximab are eligible.

You may not qualify if:

• Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, steroid requiring asthma/allergy, known HIV positive.
• Laboratory values during screening :
• Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l
• Platelet count ≤ 150 x 109 /l
• Total bilirubin ≥ 30 mmol/l
• ALP and ALAT ≥ 4x normal level
• GFR \< 60 ml/min/1.73 m2 as measured by the CKD-EPI method.
• Known or suspected CNS involvement of lymphoma
• Previous total body irradiation, or irradiation of \> 25% of the patient's bone marrow.
• Chemotherapy, immunotherapy or another investigational drug received within the last 4 weeks prior to the patient entering screening.
• Earlier treatment with radioimmunotherapy.
• Exposure to another CD37 targeting drug.
• Concurrent participation in another therapeutic treatment trial.
• Previous hematopoietic stem cell transplantation (autologous and allogenic).
• Pregnant or lactating women.

Sponsors & Collaborators

• Nordic Nanovector: lead

Study Sites (1)

Universitätsklinikum Würzburg

Würzburg, Germany

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: 23267131 BACKGROUND

• 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: 23256748 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; AIDS-Related Complex; Lymphoma; Immune System Diseases; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Neoplasms by Histologic Type; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Interventions

tetulomab tetraxetan lu-177; Lutetium; Lutetium-177

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Immunoproliferative Disorders; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Andreas Buck, Prof. MD

  Wuerzburg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 22, 2015
• First Posted: January 15, 2016
• Study Start: December 19, 2017
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2020
• Last Updated: January 10, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)