Follicular lymphoma MedDRA version: 20.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Nordic Nanovector ASA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be = 18 years at the time of signing the informed consent 2. A pre-study ECOG performance status of 0-2 3. Histologically confirmed diagnosis (by 2008 WHO classification) of indolent non-Hodgkin B-cell follicular lymphoma (grade 1, 2 or 3a) 4. 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 5. Presence of at least one bi-dimensionally measurable lesion by CT: 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 6. Normal organ and bone marrow function defined as: a. Absolute neutrophil count =1.5 x 10*9/L; b. Platelet count =150 x 10*9/L; c. Haemoglobin =9 g/dL; d. Total bilirubin =1.5 x upper limit of normal (ULN) (except patients with documented Gilbert’s syndrome [3 months 9. Negative hepatitis B, hepatitis C and HIV screening tests 10. Negative ADA test at screening for lilotomab/Betalutin 11. Women of childbearing potential (see Protocol Appendix 3) must: a. have a negative serum pregnancy test at screening and before Betalutin injection b. understand that the study medication is expected to have teratogenic risk c. agree to use, and be able to comply with, highly effective method of birth control with a Pearl Index = 1%. Contraception is required without interruption, from 4 weeks before starting study drug, throughout study drug therapy and for 12 months after end of study drug therapy, even if she has amenorrhea 12. Male patients must agree to use condoms (See Protocol Appendix 3) during intercourse throughout study drug therapy and the following 12 months 13. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination 14. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Previous haematopoietic stem cell transplantation (autologous and allogenic) 2. Evidence of histological transformation from FL to DLBCL at time of screening. 3. Previous total body irradiation 4. Chemotherapy, immunotherapy, radioimmunotherapy, or investigational therapy within 28 days before the start of study drug treatment (corticosteroid treatment at doses of = 20 mg/day, topical or inhaled corticosteroids, G-CSF or GM CSF are permitted up to 2 weeks prior to start of study treatment) or failure to recover from adverse events (AEs) associated with prior treatment 5. Patients who are receiving any other investigational medicinal products 6. Known or suspected central nervous system (CNS) involvement of lymphoma 7. History of a previous treated cancer except for the following: a. adequately treated local basal cell or squamous cell carcinoma of the skin b. cervical carcinoma in situ c. superficial bladder cancer d. localised prostate cancer undergoing surveillance or surgery e. localised breast cancer treated with surgery and radiotherapy but not including systemic chemotherapy f. other adequately treated Stage 1 or 2 cancer currently in CR 8. Pregnant or lactating women (See Protocol Appendix 3) 9. Exposure to another CD37 targeting drug 10. A known hypersensitivity to RTX, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin 11. Receipt of live, attenuated vaccine within 30 days prior to enrolment 12. Evidence of severe or uncontrolled systemic diseases: a. 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 b. Pulmonary conditions e.g. unstable or uncompensated respiratory disease c. Hepatic, renal, neurological, or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives d. 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 e. History of erythema multiforme, toxic epidermal necrolysis, or Stevens Johnson syndrome f. Cardiac conditions, including: i. history of acute coronary syndromes (including unstable angina) ii. class II, III, or IV heart failure as defined by the NYHA functional classification system iii. known uncontrolled arrhythmias (except sinus arrhythmia) in the past 24 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary • To evaluate preliminary anti-tumour activity of combination treatment based on Investigator assessment of tumour response rates ;Secondary Objective: Secondary • To evaluate the duration of tumour control in patients receiving Betalutin in combination with RTX • To characterize the safety and tolerability of Betalutin combined with RTX • To investigate the immunogenicity of Betalutin in combination with RTX ;Primary end point(s): • Responses [(overall response rate (ORR), CR, PR, stable disease (SD), progressive disease (PD)] as per Cheson 2014;Timepoint(s) of evaluation of this end point: From baseline and up to 5 years post injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Duration of response (DoR) • Progression free survival (PFS) • Time to progression (TTP) • Overall survival (OS) • Frequency and severity of adverse events (AEs) and laboratory abnormalities graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 • Monitoring of the anti-drug antibody (ADA) response towards lilotomab, Betalutin and/or RTX ;Timepoint(s) of evaluation of this end point: From baseline and up to 5 years post injection | — |
Countries
Norway
Contacts
Public ContactClinical Research Manager
Nordic Nanovector ASA
Outcome results
None listed