A Phase I/II Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.

Who is this study for? Adult patients with non-hodgkins and follicular lymphoma
What treatments are being studied? Betalutin
Status: Active, not recruiting
Location: See all (94) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This study is a phase I/II open-label study in patients with relapsed indolent NHL (Part A) or relapsed/refractory FL (Part B). Part A of the study assessed the safety and preliminary efficacy. This seamless design study now has four parts: 1) Part A, Ph I - dose escalation, 2) Part A, Ph II - dose expansion, 3) Part B, Ph II randomized - refinement of dose, and 4) Part B and C, Phase II, single-arm. As of August 7, 2020, patients are enrolling in the fourth part of the study.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

‣ Histologically confirmed (by WHO classification) relapsed incurable non- Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA, marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.

‣ Age ≥ 18 years

‣ A pre-study WHO performance status of 0-1

‣ Life expectancy should be ≥ 3 months

‣ <25% tumour cells in bone marrow biopsy

‣ Measurable disease by radiological methods

‣ Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (follicular grade I-IIIA).

• Male or female aged ≥ 18 years. 3. Received at least 2 prior anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy).

• Prior therapy must include rituximab/anti-CD20 agent and an alkylating agent. Prior exposure to other systemic anti-neoplastic agents (including idelalisib or other phosphatidylinositol 3-kinase (PI3K) inhibitors etc.) is also allowed.

• Patients must be refractory to any previous regimen containing rituximab or an anti-CD20 agent, defined as: no response (no CR/PR) during therapy, or a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).

• WHO performance status of 0-2. 7. Life expectancy of ≥ 3 months. 8. Bone marrow tumour infiltration < 25% (in biopsy taken from a site not previously irradiated).

• Measurable disease by CT or MRI: longest diameter (LDi) > 1.5 cm for nodal lesion, LDi > 1.0 cm for extra nodal lesion within 28 days prior to start of treatment.

⁃ ANC ≥ 1.5 x 109/L. 11. Platelet count ≥ 100 x 109/L . 12. Haemoglobin ≥ 9.0 g/dL. 13. Total bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with documented Gilbert's syndrome [< 3.0 mg/dL]).

⁃ Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or ALP ≤ 2.5 x ULN (or ≤ 5.0 x ULN with liver involvement by primary disease).

⁃ Adequate renal function as demonstrated by a serum creatinine < 1.5 x ULN. 16. Women of childbearing potential must:

‣ understand that the study medication is expected to have teratogenic risk.

‣ have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening.

‣ commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin a highly effective method of birth control with a Pearl-Index < 1%, without interruption, from 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea. Apart from abstinence, highly effective methods of birth control are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).

‣ ii. Progestogen-only hormonal contraception associated with inhibition of ovulation ((oral, injectable, implantable) iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomised partner. 17. Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.

⁃ The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination.

⁃ The patient has been fully informed about the study and has signed the informed consent form.

⁃ Negative HAMA test at screening. 21. Negative Hepatitis B (negative HBsAG and anti-HBC), Hepatitis C and HIV test at screening

Locations
United States
Arkansas
University Of Arkansas For Medical Sciences
Little Rock
California
Pacific Shores Medical Group
Long Beach
University of California, San Francisco (UCSF)
San Francisco
Florida
Boca Raton Regional Hospital
Boca Raton
Illinois
Loyola University Medical Center
Maywood
Kentucky
Norton Cancer Institute
Louisville
Louisiana
Ochsner Clinic Foundation
New Orleans
North Carolina
Duke University Medical Center
Durham
New York
Stony Brook University Medical Center
Stony Brook
Oregon
Oregon Health & Science University
Portland
Pennsylvania
University of Pennsylvania
Philadelphia
University of Pittsburgh Medical Center
Pittsburgh
West Penn Hospital
Pittsburgh
Texas
Baylor College of Medicine
Dallas
Other Locations
Australia
Royal Hobart Hospital
Hobart
Austria
Medizinische Universitaet Innsbruck
Innsbruck
Medizinische Universität Wien - AKH Wien, Universitaetsklinik fuer Innere Medizin I
Wien
Belgium
Universitair Ziekenhuis Gent (UZ Gent)
Gent
CH Jolimont
La Louvière
UZ Leuven
Leuven
Canada
London Health Sciences Centre
London
Sault Area Hospital
Sault Ste Marie
Princes Margaret Cancer Centre
Toronto
Croatia
Clinical Hospital Centre Zagreb
Zagreb
Denmark
Aarhus Universitetshospital
Aarhus
Odense Univerisity Hospital
Odense
Finland
Helsinki University Hospital Comprehensive Cancer Center
Helsinki
Central Hospital Of Central Finland
Jyväskylä
France
Institut Bergonie
Bordeaux
Chu Grenoble - Hopital Michallon
Grenoble
AP-HP La Pitié salpétrière
Paris
Hôpital Saint Louis
Paris
Centre Hospitalier Lyon Sud
Pierre-bénite
Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau
Tours
Hungary
Orszagos Onkologiai Intezet, A-Belgyogyaszati Onkologiai Osztaly
Budapest
Semmelweis Egyetem, I Belgyogyaszati Klinika, Hematologiai Osztaly
Budapest
Ireland
Mater Misericordiae University Hospital
Dublin
St James's Hospital
Dublin
University Hospital Galway
Galway
Israel
Haemek Medical Center
Afula
Asaf Harofeh Medical Center
Be'er Ya'aqov
Bnai Zion Medical Center (BZMC)
Haifa
Rambam Health Care Campus (RHCC)
Haifa
יHadassah Ein Karem Medical Center
Jerusalem
Sourasky Medical Center
Tel Aviv
Italy
SS Antonio & Biagio and C. Arrigo Hospital
Alessandria
Istituto di Ematologia ed Oncologia Medica L. & A. Seragnoli-Policlinico S. Orsola Malpighi
Bologna
Universita Degli Studi Di Firenze-Azienda Ospedaliero-Universitaria Careggi (AOUC)
Firenze
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
Meldola
Istituto Europeo di Oncologia (IEO)
Milano
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS
Reggio Emilia
AO Ordine Mauriziano di Torino
Torino
Netherlands
University Medical Center Groningen
Groningen
Norway
Haukeland Universitetssjukehus
Bergen
The Norwegian Radium Hospital
Oslo
St Olav Hospital
Trondheim
Poland
Szpital Morski Im.Pck W Gdynia
Gdynia
Pratia MCM Kraków
Krakow
Centrum Onkologii
Warszawa
Republic of Korea
Chonbuk National University Hospital
Jeonju
Samsung Medical Center
Seoul
Ulsan University Hospital
Ulsan
Singapore
National University Hospital
Singapore
Spain
Corporacio Sanitaria Parc Taulí
Barcelona
Hospital Universitario Puerta del Mar
Cadiz
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda
Complexo Hospitalario Universitario de Ourense
Ourense
Clinica Universidad De Navarra
Pamplona
Hospital Clinico Universitario de Salamanca
Salamanca
Hospital Universitario Virgen Macarena
Seville
Health Research Institute La Fe - Hospital La Fe
Valencia
Hospital Universitario Doctor Peset
Valencia
Sweden
Cancercentrum -Center of Oncology
Umeå
Switzerland
Kantonsspital Graubünden
Chur
Turkey
Cukurova Universitesi Tip Fakültesi, Ic Hastaliklari Anabilim Dali
Adana
Ankara Onkoloji Egitim ve Arastirma Hastanesi
Ankara
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi Ic
Ankara
Hacettepe University Oncology Hospital
Ankara
Eskisehir Osmangazi Universitesi Tip Fakultesi Ic Hastaliklar
Eskişehir
Istanbul Universitesi Istanbul Tip Fakultesi
Fatih
Ege Universitesi Tip Fakültesi
İzmir
Celal Bayar Universitesi Tip Fakultesi
Manisa
Ondokuz Mayis Universitesi
Samsun
Gaziantep Universitesi Sahinbey Arastirma ve Uygulama
Şehitkamil
United Kingdom
Bristol Haematology and Oncology Centre
Bristol
Western General Hospital
Edinburgh
Beatson West of Scotland Cancer Centre
Glasgow
Imperial College Healthcare NHS Trust, Hammersmith Hospital
London
University College London Hospitals Nhs Foundation Trust
London
The Christie NHS Foundation Trust
Manchester
Derriford Hospital
Plymouth
Dorset Cancer Centre Poole Hospital
Poole
The Royal Marsden NHS Foundation Trust
Sutton
Time Frame
Start Date: December 2012
Estimated Completion Date: November 2022
Participants
Target number of participants: 191
Treatments
Experimental: Part A, Arm 1: with lilotomab pre-dosing
Betalutin, 10 MBq/kg b.w. in escalated doses with lilotomab pre-dosing.~COMPLETED enrolment into this arm
Experimental: Part A, Arm 2: without pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing.~COMPLETED enrolment into this arm
Experimental: Part A, Arm 3: with rituximab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing.~COMPLETED enrolment into this arm
Experimental: Part A, Arm 4: with higher dose lilotomab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with a higher dose lilotomab pre-dosing regimen.~COMPLETED enrolment into this arm
Experimental: Part A, Arm 5: with intermediate dose lilotomab pre-dosing
Betalutin, 20 MBq/kg b.w. with an intermediate dose lilotomab pre-dosing regimen.~COMPLETED enrolment into this arm
Experimental: Part B and Part C
Available dosing arm - '40/15'~Completed enrolment
Authors
Don Stevens, Laura Finn, Matthew McKinney, Michael Schuster, Scott Smith, Kathleen Dorritie, Spencer Bachow, Daniel Pryma, Cyrus Khan, Erik Mittra, Andre Kiem Di Liem, Appalanaidu Sasapu, Arne Kolstad, Miguel Pampaloni, Christopher Maisel
Sponsors
Leads: Nordic Nanovector
Collaborators: ICON Clinical Research

This content was sourced from clinicaltrials.gov

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