Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL

Phase 1

Completed

Conditions: Non Hodgkin Lymphoma
Follicular Lymphoma
Relapsed Follicular Lymphoma

Interventions: Drug: 10 MBq/kg Betalutin
Drug: 15 MBq/kg Betalutin

Registration Number: NCT03806179

Lead Sponsor: Nordic Nanovector

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
10 MBq/kg Betalutin with rituximab treatment	10 MBq/kg Betalutin	10 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years
15 MBq/kg Betalutin with rituximab treatment	15 MBq/kg Betalutin	15 MBq/kg Betalutin administered with lilotomab pre-dose on day 0; rituximab administered weekly x 4 doses from day 7, then every 3 months for 2 years

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability: Frequency and Severity of Adverse Events (CTCAE v4.03)	12 weeks	Safety and tolerability of Betalutin in combination with rituximab as determined by the frequency and severity of adverse events (CTCAE v4.03) in the first 12 weeks after Betalutin

Secondary Outcome Measures

Name	Time	Method
Preliminary Anti-tumour Activity	25 months	Best overall response of combination treatment using tumour responses based on CT and PET/CT imaging (classified as as complete response, partial response, no response/stable disease or progressive disease as described in "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification")