Non-Hodgkin B-cell lymphoma Part A: Relapsed indolent Non-Hodgkin B-cell lymphoma Part B: Relapsed follicular lymphoma Part C: Relapsed indolent Non-Hodgkin B-cell lymphoma MedDRA version: 22.0 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: Part A (phase I and phase IIa) and Part C (phase IIa Pharmacokinetics Cohort): 1. Histologically confirmed (by 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. 2. Age = 18 years. 3. Part A: A pre-study WHO performance status of 0-1, Part C: WHO performance status of 0-2. 4. Life expectancy should be = 3 months. 5. 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 x 109/L. 11. Platelet count = 100 x 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 x upper limit of normal (ULN) (except patients with documented Gilbert’s syndrome [< 3.0 mg/dL]). 14. Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or ALP = 2.5 x ULN (or = 5.0 x ULN with liver involvement by pr
Exclusion criteria
Exclusion criteria: Part A and Part C (phase IIa Pharmacokinetic Cohort): 1. Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, uncontrolled asthma/allergy requiring systemic steroids, known HIV positive. 2. Laboratory values within 15 days pre-registration: a. Absolute Neutrophil Counts (ANC) = 1.5 x 109 /l. b. Part A: Platelet count = 150 x 109 /L, Part C: Platelet count 1.5xULN (except patients with documented Gilbert´s syndrome [=3.0 mg/dL]) (Part C only). d. ALP and ALAT = 4x normal level (Part A only). Aspartate transaminase (AST), ALT or ALP >2.5xULN (or >5.0xULN with liver involvement by primary disease). (Part C only). e. Creatinine = 115 µmol/l (men), 97 µmol/l (women) (Part A only). Serum creatinine =1.5xULN (Part C only). f. Haemoglobin 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From baseline until 60 months post injection;Main Objective: Part A: Phase I (Arms 1, 2, 3, 4 and 5): To define MTD of Betalutin Phase IIa: To explore tumour response rates in patients receiving Betalutin. Part B (FL phase IIb "PARADIGME"): Randomised section of Part B To evaluate the efficacy of the "40/15" dose regimen (40 mg lilotomab / 15 MBq/kg Betalutin) compared with "100/20" dose regimen (100 mg/m2 lilotomab/ 20 MBq/kg Betalutin) based on an Independent Review Committee (IRC) assessment of tumour response rates in adult patients with relapsed rituximab/anti-CD20-refractory follicular lymphoma. Selected regimen for further development To evaluate the ORR of the regimen selected for further development based on the IRC assessment of tumour response rates in adult patients with relapsed rituximab/anti-CD20 refractory FL. Part C, phase IIa (Pharmacokinetic Cohort): To further characterise the pharmacokinetics of Betalutin (total radioactivity measurements in blood) and total lilotomab antibodies (antibodies measured in serum);Secondary Objective: Part A: Phase I (Arms 1, 2, 3, 4 and 5): To establish recommended dose of Betalutin for phase IIa, investigate safety, toxicity, biodistribution, pharmacokinetics and to explore the efficacy. Phase IIa: to confirm the recommended dose of Betalutin from Part A, phase I, investigate safety and toxicity, estimate progression free survival and overall survival, quality of life. Part B: To compare the "40/15" and "100/20" treatment regimens in the randomised section and to evaluate the regimen selected for further development, in terms of the following: Efficacy • ORR by investigator assessment • CRR by independent review and investigator assessment • DoR by independent review and investigator assessment • DoCR by independent review and investigator assessment • PFS by independent review and investigator assessment • OS Safety • incidence and severity of events (AEs). Part C, | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From baseline and up to 5 years post injection;Secondary end point(s): Part A: • Incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukaemia, myelodysplastic syndrome, and aplastic anaemia). • Overall survival. • Estimation of whole-body retention of radioactivity at each imaging time post-injection. • Estimation of the individual organ uptake/retention of radioactivity at each imaging time-point after injection. • Estimate retention of administered radioactivity in blood. • Calculation of estimated absorbed radiation dose to target organs. • Tumour response rate. • Tumour response duration. • Progression-free survival • Performance status defined as improvement or worsening, respectively, by 1-point or more on the ECOG scale from the baseline value • Quality of life (QoL) assessed using Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaire Part B: • Incidence and severity of AEs Efficacy: • ORR by investigator assessment. • CRR by independent review and investigator assessment. • DoR by independent review and investigator assessment. • DoCR by independent review and investigator assessment. • PFS by independent review and investigator assessment. • OS. • Change from baseline in the sum of the product of the greatest perpendicular diameters (SPD) of target lymph nodes as documented radiographically. Part C: • Incidence and severity of AEs. • Tumour response rate. • Tumour response duration. • OS. | — |
Countries
Australia, Austria, Belgium, Croatia, Czech Republic, Denmark, European Union, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactInformation Desk
Nordic Nanovector ASA
Outcome results
None listed