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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Dose finding study, starting on 10 MBq/kg b.w. Betalutin® (lutetium (177Lu)-lilotomab satetraxetan), single injection with lilotomab pre-dosing.
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
Number of Participants With DLTs to Determine the MTD
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
Time frame: 12 weeks
The Best Overall Tumour Response
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.
Time frame: 3 months - 2 years
Dosimetry
Dosimetry will be evaluated by the estimated absorbed radiation dose to target organs.
Time frame: 3 weeks
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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