Clinical trial NCT03806179: Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL
Official title: A Phase 1b Open-label Study of Betalutin in Combination With Rituximab in Patients With Relapsed/Refractory Follicular Lymphoma (Archer-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Hodgkin Lymphoma
Follicular Lymphoma
Relapsed Follicular Lymphoma
Keywords: Radioimmunotherapy
Lu-177
Betalutin
Phase 1b
Combination
Rituximab
Lead sponsor: Nordic Nanovector
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2019-01-16
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a Phase 1b, open-label, single arm dose escalation study of Betalutin followed by rituximab in patients with previously treated follicular lymphoma. The purpose of this study is to characterise the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of Betalutin in combination with rituximab.


Eligibility criteria: Inclusion Criteria:

* Patient must be ≥18 years at the time of signing the informed consent
* ECOG performance status of 0-2
* Histologically confirmed diagnosis (by 2008 World Health Organization \[WHO\] classification) of follicular lymphoma (grade 1, 2 or 3a)
* At least one (but not more than 3) prior regimens with an anti-CD20 antibody (alone or in combination with chemotherapy), with documented relapsed, refractory disease (must not be anti-CD20 antibody-refractory) or PD
* Presence of at least one bi-dimensionally measurable lesion by CT or MRI: longest diameter (LDi) \>1.5 cm for a nodal lesion; LDi \>1.0 cm for an extranodal lesion within 28 days prior to start of treatment
* 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 \[\<3.0 mg/dL\]);
  5. 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 within the upper limit of normal range
* Bone marrow involvement by lymphoma \<25%
* Life expectancy \>3 months
* Negative hepatitis B, hepatitis C and human immunodeficiency virus (HIV) screening tests
* Patients must agree to use effective contraception for 12 months following last study drug administration

Exclusion criteria:

* Previous haematopoietic stem cell transplantation (autologous and allogenic)
* Evidence of histological transformation from FL to DLBCL at time of screening.
* Previous total body irradiation
* Chemotherapy, immunotherapy or investigational therapy within 28 days before the start of study drug administration (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 study treatment) or failure to recover from AEs associated with prior treatment
* Previous treatment with radioimmunotherapy
* Patients who are receiving any other investigational medicinal products
* Known or suspected central nervous system (CNS) involvement of lymphoma
* 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 or localised prostate cancer undergoing surveillance or surgery
  4. localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy
  5. other adequately treated Stage 1 or 2 cancer currently in CR
* Pregnant or lactating women
* Exposure to another CD37 targeting drug
* A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in RTX, lilotomab or Betalutin
* Receipt of live, attenuated vaccine within 30 days prior to enrolment
* Evidence of severe or uncontrolled systemic diseases (e.g. ongoing infection, respiratory, cardiac, hepatic or psychiatric conditions) which in the Investigator's opinion would compromise the protocol objectives

Primary outcomes:
measure: Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03)
timeFrame: 12 weeks
Secondary outcomes:
measure: Preliminary Anti-tumour Activity
timeFrame: 25 months
Other outcomes:
Locations:
city: Ostrava-
country: Czechia
facility: Klinika Hematoonkologie
state: Porubá
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Alexander Fosså, MD.PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Repetto-Llamazares AHV, Malenge MM, O'Shea A, Eiriksdottir B, Stokke T, Larsen RH, Dahle J. Combination of 177 Lu-lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non-Hodgkin's lymphoma. Eur J Haematol. 2018 Oct;101(4):522-531. doi: 10.1111/ejh.13139. Epub 2018 Aug 31.
citation: Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.