Fase di studio: II
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Terza/N linea
Criteri di inclusione:
1. Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (grade I-IIIA).
2. Male or female aged ≥18 years.
3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.
4. Prior therapy must have included a rituximab/anti-CD20 agent and an alkylating agent – which may be been administered in separate regimens.
5. Patients must be refractory to any at least one previous regimen that contained rituximab or an anti-CD20 agent, with refractoriness defined as: i. no response (no CR or PR) during therapy, or ii. a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).
6. WHO performance status of 0-2.
7. Life expectancy of ≥3 months.
8. Bone marrow tumour infiltration <25% (in biopsy taken from a site not previously irradiated).
9. Measurable disease by CT or MRI: longest diameter (LDi) >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 ≥1.5×109 /L.
11. Platelet count ≥100×109 /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×upper limit of normal (ULN) (except patients with documented Gilbert’s syndrome [<3.0 mg/dL]).
14. Liver enzymes: AST; ALT or ALP ≤2.5×ULN (or ≤5.0×ULN with liver involvement by primary disease).
15. Adequate renal function as demonstrated by a serum creatinine <1.5×ULN
16. Women of childbearing potential must: a) understand that the study medication is expected to have teratogenic risk. b) have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening. c) commit to continued abstinence from heterosexual intercourse
17. Male patients must agree to use condoms during intercourse throughout study treatment administration and for 12 months following administration of Betalutin.
18. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination.
19. The patient has been fully informed about the study and has signed the informed consent form
Criteri di esclusione:
1.Prior hematopoietic allogenic stem cell transplantation.
2. Patients with a prior autologous SCT are excluded unless at least two years have elapsed since transplantation.
3. Evidence of histological transformation from FL to diffuse large B-cell lymphoma (DLBCL) at time of screening (transformation to grade IIIB that was successfully treated with recurrence of grade I-IIIA initial clone is accepted).
4. Previous total body irradiation.
5. Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other systemic agent including any investigational agent) within 4 weeks prior to start of study treatment (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 rituximab)..
6. Patients who are receiving any other investigational medicinal products.
7. Patients with known or suspected CNS involvement of lymphoma.
8. History of malignancy other than FL within 5 years prior to screening( i.e. patients with cancer diagnosed within 5 years prior to screening or who were diagnosed prior to 5 years and were not in CR or were on treatment within 5 years prior to screening), with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
9. Pregnant or breastfeeding women.
10. Exposure to another CD37 targeting drug.
11. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.
12. Has received a live-attenuated vaccine within 30 days prior to enrolment.
13. 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 in the previous 24 weeks (before date of consent), including i. history of acute coronary syndromes (including unstable angina). ii. class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. iii. known uncontrolled arrhythmias (except sinus arrhythmia).
Numero di pazienti previsti:
Schema di trattamento:
177 Lutetium (177Lu)-lilotomab satetraxetan (Betalutin)and lilotomab
Trattamento di controllo:
Obiettivi primari dello studio:
To evaluate the overall response rate (ORR) in adult patients with relapsed rituximab/anti-CD20 refractory FL
Obiettivi secondari dello studio:
-ORR by investigator assessment
-Complete response rate (CRR) by independent review and investigator assessment
-Duration of response (DoR) by independent review and investigator assessment
-Duration of complete response (DoCR) by independent review and investigator assessment
-Progression free survival (PFS) by independent review and investigator assessment
-Incidence and severity of adverse events (AEs)
Data di inizio dell'arruolamento: 01.12.2012
AO SS Antonio e Biagio e C. Arrigo
Via Venezia 16 - 15100 Alessandria - AL
Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO
Riferimento: Prof. Pier Luigi Zinzani
IRCCS - IRST Meldola Dino Amadori
Via P. Maroncelli 40 - 47014 Meldola - FC
Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
AUSL/IRCCS di Reggio Emilia
Viale Risorgimento 80 - 42123 Reggio nell'Emilia - RE
Riferimento: Prof. Stefano Luminari
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Numero di iscrizione a registro: 2011-000033-36
Data di inserimento: 17.06.2022
Policlinico S.Orsola Malpighi, Bologna (Ematologia)
Riferimento: Prof. Pier Luigi Zinzani