Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL
Condition: Non Hodgkin Lymphoma; Follicular Lymphoma; Relapsed Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: 10 MBq/kg Betalutin; 15 MBq/kg Betalutin
Intervention description: 10 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2; 15 MBq/kg Betalutin, lilotomab 40mg, rituximab 375 mg/m2
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radioimmunotherapy; Lu-177; Betalutin; Phase 1b; Combination; Rituximab

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