Non Hodgkin Lymphoma Clinical Trial

A Phase 1/2 Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma

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.

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Full Description

Part A of the study was a Phase 1/2a study to assess the safety and preliminary efficacy of different treatment regimens of Betalutin with expansion at the candidate recommended Phase 2 doses. Part B was a dedicated Phase 2b randomized substudy to further assess the efficacy and safety of the candidate recommended Phase II doses. Part C was a Phase 2a fixed dose expansion cohort planned to obtain supplementary pharmacokinetic data.

View Eligibility Criteria

Eligibility Criteria

Part A and Part C:

Inclusion Criteria:

Histologically confirmed (by World Health Organization [WHO] classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA (for Part C, this excludes patients meeting Part B criteria, who should enter Part B), marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.
Age ≥ 18 years.
Part A: A pre-study WHO performance status of 0-1; Part C: WHO performance status of 0-2.
Life expectancy should be ≥3 months.
<25% tumour cells in bone marrow biopsy (biopsy taken from a site not previously irradiated).
Measurable disease by radiological methods.

Women of childbearing potential must:

understand that the study medication is expected to have teratogenic risk.
have a negative pregnancy test.
agree to use, and be able to comply with, effective contraception without interruption, 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.
Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.
Patients previously treated with native rituximab are eligible.
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.

Exclusion Criteria:

Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, uncontrolled asthma/allergy requiring systemic steroids, known to be human immunodeficiency virus (HIV) positive.

2. Laboratory values within 15 days pre-registration:

Absolute neutrophil counts (ANC) ≤1.5×109/L.
Part A: Platelet count ≤150×109/L; Part C: Platelet count <150×109/L. For Part C, criteria 2a and 2b must be satisfied within 72 hours of the administration of rituximab
Total bilirubin ≥30 mmol/L (Part A only). Total bilirubin > 1.5×ULN (except patients with documented Gilbert's syndrome [≥3.0 mg/dL]) (Part C only).

Alkaline phosphatase (ALP) and alanine transaminase (ALT) ≥4×normal level (Part A only).

Aspartate transaminase (AST), ALT or ALP >2.5×ULN (or >5.0×ULN with liver involvement by primary disease). (Part C only).

Creatinine ≥115 µmol/L (men), 97 µmol/L (women) (Part A only). Serum creatinine ≥1.5×ULN (Part C only).

Haemoglobin <9.0 g/dL (Part C only). 3. Known central nervous system (CNS) involvement of lymphoma. 4. Previous total body irradiation. 5. Positive test for human anti-murine antibody (HAMA) at screening. 6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pre treatment with rituximab is allowed.

7. Pregnant or lactating women. 8. Previous hematopoietic stem cell transplantation (autologous and allogenic). 9. Part A: Previous treatment with radioimmunotherapy. Part C: Not applicable. 10. Actively participating in another study or received an IMP within 4 weeks prior to enrolment.

11. Receipt of live-attenuated vaccine within 30 days prior to enrolment. 12. Part A and Part C: Test positive for hepatitis B (HBsAg and anti-HBc). Part C only: Test positive for hepatitis C and human immunodeficiency virus (HIV).

13. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.

Part B:

Inclusion Criteria:

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

2. Male or female aged ≥18 years. 3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.

4. Prior therapy must have included a rituximab/anti-CD20 agent and an alkylating agent - which may be been administered in separate regimens.

5. Patients must be refractory to any at least one previous regimen that contained rituximab or an anti CD20 agent, with refractoriness defined as:

i. no response (no CR or PR) during therapy, or ii. 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).

6. 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).

9. Measurable disease by CT or MRI: longest diameter (LDi) >1.5 cm for nodal lesion, LDi >1.0 cm for extra nodal lesion on an assessment performed during the screening period.

Criteria 10 and 11 must be satisfied within 72 hours of the administration of rituximab:

10. ANC ≥1.5×109/L. 11. Platelet count ≥100×109/L.

Criteria 12 to 15 must be verified at time of eligibility review within 2 weeks prior to rituximab administration:

12. Haemoglobin ≥9.0 g/dL. 13. Total bilirubin ≤1.5×upper limit of normal (ULN) (except patients with documented Gilbert's syndrome [<3.0 mg/dL]).

14. Liver enzymes: AST; ALT or ALP ≤2.5×ULN (or ≤5.0×ULN with liver involvement by primary disease).

15. Adequate renal function as demonstrated by a serum creatinine <1.5×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 treatment administration and for 12 months following administration of Betalutin.

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

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

20. Negative HAMA test at screening. 21. Negative test at screening for Hepatitis B (negative HBsAg and anti-HBc), Hepatitis C and HIV.

Exclusion Criteria

Prior hematopoietic allogenic stem cell transplantation.
Patients with a prior autologous SCT are excluded unless at least two years have elapsed since transplantation.
Evidence of histological transformation from FL to diffuse large B-cell lymphoma (DLBCL) at time of screening (transformation to grade IIIB that was successfully treated with recurrence of grade I-IIIA initial clone is accepted).
Previous total body irradiation.
Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other systemic agent including any investigational agent) within 4 weeks prior to start of study treatment (corticosteroid treatment at doses of ≤ 20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] are permitted up to 2 weeks prior to start of rituximab)..
Patients who are receiving any other investigational medicinal products.
Patients with known or suspected CNS involvement of lymphoma.
History of malignancy other than FL within 5 years prior to screening( i.e. patients with cancer diagnosed within 5 years prior to screening or who were diagnosed prior to 5 years and were not in CR or were on treatment within 5 years prior to screening), with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

.9. Pregnant or breastfeeding women. 10. Exposure to another CD37 targeting drug. 11. A known hypersensitivity to rituximab, lilotomab, 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 enrolment. 13. Evidence of severe or uncontrolled systemic diseases:

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.
Pulmonary conditions e.g. unstable or uncompensated respiratory disease.
Hepatic, renal, neurological, or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives.
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.
History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome.
Cardiac conditions in the previous 24 weeks (before date of consent), including

i. history of acute coronary syndromes (including unstable angina). ii. class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

iii. known uncontrolled arrhythmias (except sinus arrhythmia).

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

191

Study ID:

NCT01796171

Recruitment Status:

Completed

Sponsor:

Nordic Nanovector

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There are 42 Locations for this study

See Locations Near You

University Of Arkansas For Medical Sciences
Little Rock Arkansas, 72205, United States
Pacific Shores Medical Group
Long Beach California, 90813, United States
University of California, San Francisco (UCSF)
San Francisco California, 94143, United States
Boca Raton Regional Hospital
Boca Raton Florida, 33486, United States
Loyola University Medical Center
Maywood Illinois, 60153, United States
Norton Cancer Institute
Louisville Kentucky, 40207, United States
Ochsner Clinic Foundation
New Orleans Louisiana, 70121, United States
Stony Brook University Medical Center
Stony Brook New York, 11794, United States
Duke University Medical Center
Durham North Carolina, 27710, United States
Oregon Health & Science University
Portland Oregon, 97239, United States
University of Pennsylvania
Philadelphia Pennsylvania, 19104, United States
West Penn Hospital
Pittsburgh Pennsylvania, 15224, United States
University of Pittsburgh Medical Center
Pittsburgh Pennsylvania, 15232, United States
Baylor College of Medicine
Dallas Texas, 75246, United States
Royal Hobart Hospital
Hobart , 7000, Australia
Medizinische Universitaet Innsbruck
Innsbruck , 6020, Austria
Medizinische Universität Wien - AKH Wien, Universitaetsklinik fuer Innere Medizin I
Wien , 1090, Austria
Universitair Ziekenhuis Gent (UZ Gent)
Gent , 9000, Belgium
CH Jolimont
La Louvière , , Belgium
UZ Leuven
Leuven , 3000, Belgium
London Health Sciences Centre
London , N6A 5, Canada
Sault Area Hospital
Sault Ste Marie , P6B 0, Canada
Princes Margaret Cancer Centre
Toronto , M5G 2, Canada
Clinical Hospital Centre Zagreb
Zagreb , 10 00, Croatia
University Hospital Olomouc
Olomouc , 779 0, Czechia
FNsP Ostrava
Ostrava-Poruba , 708 5, Czechia
Aarhus Universitetshospital
Aarhus , DK-80, Denmark
Odense Univerisity Hospital
Odense , DK-50, Denmark
Helsinki University Hospital Comprehensive Cancer Center
Helsinki , , Finland
Central Hospital Of Central Finland
Jyväskylä , , Finland
Institut Bergonie
Bordeaux , , France
Chu Grenoble - Hopital Michallon
Grenoble , , France
Hôpital Saint Louis
Paris , 75010, France
AP-HP La Pitié salpétrière
Paris , 75013, France
Centre Hospitalier Lyon Sud
Pierre-Bénite , , France
Centre Hospitalier Regional Universitaire de Tours (CHRU de Tours) - Hopital Bretonneau
Tours , , France
Orszagos Onkologiai Intezet, A-Belgyogyaszati Onkologiai Osztaly
Budapest , , Hungary
Semmelweis Egyetem, I Belgyogyaszati Klinika, Hematologiai Osztaly
Budapest , , Hungary
Mater Misericordiae University Hospital
Dublin , , Ireland
St James's Hospital
Dublin , , Ireland
University Hospital Galway
Galway , , Ireland
Haemek Medical Center
Afula , , Israel
Asaf Harofeh Medical Center
Be'er Ya'aqov , , Israel
Bnai Zion Medical Center (BZMC)
Haifa , , Israel
Rambam Health Care Campus (RHCC)
Haifa , , Israel
יHadassah Ein Karem Medical Center
Jerusalem , , Israel
Sourasky Medical Center
Tel Aviv , , Israel
SS Antonio & Biagio and C. Arrigo Hospital
Alessandria , , Italy
"Istituto di Ematologia ed Oncologia Medica "" L. & A. Seragnoli""-Policlinico S. Orsola Malpighi"
Bologna , 40138, Italy
Universita Degli Studi Di Firenze-Azienda Ospedaliero-Universitaria Careggi (AOUC)
Firenze , 50134, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
Meldola , , Italy
Istituto Europeo di Oncologia (IEO)
Milano , , Italy
"Istituto Nazionale Tumori Fondazione G. Pascale"
Napoli , , Italy
Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS
Reggio Emilia , , Italy
AO Ordine Mauriziano di Torino
Torino , , Italy
Chonbuk National University Hospital
Jeonju , , Korea, Republic of
Samsung Medical Center
Seoul , , Korea, Republic of
Ulsan University Hospital
Ulsan , , Korea, Republic of
University Medical Center Groningen
Groningen , , Netherlands
Haukeland Universitetssjukehus
Bergen , , Norway
The Norwegian Radium Hospital
Oslo , 0310, Norway
St Olav Hospital
Trondheim , 7006, Norway
Szpital Morski Im.Pck W Gdynia
Gdynia , , Poland
Pratia MCM Kraków
Krakow , 50-51, Poland
Centrum Onkologii
Warszawa , 02-09, Poland
National University Hospital
Singapore , , Singapore
Corporacio Sanitaria Parc Taulí
Barcelona , , Spain
Hospital Universitario Puerta del Mar
Cadiz , , Spain
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda , , Spain
Complexo Hospitalario Universitario de Ourense
Ourense , , Spain
Clinica Universidad De Navarra
Pamplona , , Spain
Hospital Clinico Universitario de Salamanca
Salamanca , , Spain
Hospital Universitario Virgen Macarena
Seville , , Spain
Health Research Institute La Fe - Hospital La Fe
Valencia , 46020, Spain
Hospital Universitario Doctor Peset
Valencia , 46026, Spain
Cancercentrum -Center of Oncology
Umeå , , Sweden
Kantonsspital Graubünden
Chur , , Switzerland
Cukurova Universitesi Tip Fakültesi, Ic Hastaliklari Anabilim Dali
Adana , , Turkey
Ankara Onkoloji Egitim ve Arastirma Hastanesi
Ankara , , Turkey
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi Ic
Ankara , , Turkey
Hacettepe University Oncology Hospital
Ankara , , Turkey
Eskisehir Osmangazi Universitesi Tip Fakultesi Ic Hastaliklar
Eskişehir , , Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
Fatih , , Turkey
Ege Universitesi Tip Fakültesi
İzmir , , Turkey
Celal Bayar Universitesi Tip Fakultesi
Manisa , , Turkey
Ondokuz Mayis Universitesi
Samsun , , Turkey
Gaziantep Universitesi Sahinbey Arastirma ve Uygulama
Şehitkamil , , Turkey
Dorset Cancer Centre Poole Hospital
Poole Dorset, BH15 , United Kingdom
Bristol Haematology and Oncology Centre
Bristol , BS2 8, United Kingdom
Western General Hospital
Edinburgh , , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow , G12 0, United Kingdom
Imperial College Healthcare NHS Trust, Hammersmith Hospital
London , W12 0, United Kingdom
University College London Hospitals Nhs Foundation Trust
London , , United Kingdom
The Christie NHS Foundation Trust
Manchester , M20 4, United Kingdom
Derriford Hospital
Plymouth , , United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton , , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

191

Study ID:

NCT01796171

Recruitment Status:

Completed

Sponsor:


Nordic Nanovector

How clear is this clinincal trial information?

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