Clinical trial NCT03804372: The Incidence of Hepatitis B in Diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive Treated With Rituximab, Chemotherapy and Tenofovir Alafenamide
Official title: Prospective Study on the Incidence of Hepatitis B Virus Reactivation in Untreated Patients With Diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive Treated With Rituximab, Chemotherapy and Tenofovir Alafenamide
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Large-B-cell Diffuse Lymphoma
Chronic Lymphoid Leukemia
Keywords: diffuse Large B-Cell Lymphoma
chronic Lymphoid Leukemia HBsAg-positive
Rituximab
chemotherapy
alafenamide
hepatitis B virus reactivation
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2019-01-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, we will evaluate the incidence of hepatitis B virus reactivation within the first 6 months of treatment with rituximab, standard chemotherapy and TAF in patients with diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive.

Detailed description: This is a prospective, multicenter, interventional, single arm, evaluating the incidence of hepatitis B virus (HBV) reactivation within the first 6 months treatment period in HBsAg positive patients treated for DLBCL/Chronic Lymphoid Leukemia with Rituximab, standard chemotherapy, and TAF.

Approximate duration of the recruitment period based on the number of patients available The duration of the recruitment period has been estimated at 12 months.

Patients will receive Rituximab+Chemotherapy+TAF for 6 months, followed by TAF as monotherapy for further 12 months. All subjects will receive TAF 1-3 weeks before Rituximab+Chemotherapy and withdrawn 12 months after the completion of chemotherapy. Then patients will be also observed for further12 months

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent according to ICH/EU/GCP and national local laws.
* Male/non-pregnant/non-lactating female subjects \>18 years old with newly diagnosed DLBCL/Chronic Lymphoid Leukemia who are going to receive treatment with rituximab in combination with chemotherapy.
* HBsAg positivity, serum HBV-DNA negative or positive (\<2000/IU), and normal liver function, including alanine aminotransferase(ALT), aspartate aminotransferase(AST) and bilirubin. (inactive carriers).
* No previous treatment with antiviral drugs for HBV infection.
* Patients with satisfactory renal function.

Exclusion Criteria:

* Hepatic insufficiency for any reason
* History of other liver diseases such as hepatitis C, D, autoimmune hepatitis, primary biliary cirrhosis, Wilsons' disease
* Positive viral markers, such as IgM antibody to hepatitis A virus, hepatitis C virus, IgG antibody to hepatitis D virus, IgM antibody to hepatitis E virus, or antibody to HIV
* Pregnant or breastfeeding women
* Other major systemic diseases, such as active infection, significant cardiac disease, neurological deficit or psychiatric disorder, that the investigators consider being a significant risk
* Patients with moderate or severe renal failure.
* Intolerance to any of the components of the therapeutic regimen. Treatment with any investigational medicinal product (unapproved) in the last 30 days.
* Any other disorder that, in the investigator's opinion, makes the patient ineligible for recruitment or that could interfere in his/her participation or in the conclusion of the study.

Primary outcomes:
measure: Percentage of patients presenting hepatitis B virus reactivation
timeFrame: Within 6 months following the start of treatment
Secondary outcomes:
measure: Percentage of patients presenting hepatitis B virus reactivation
timeFrame: After 12 months following the study entry and start of treatment
measure: Number of patients stratified by DLBCL and Chronic Lymphoid Leukemia with hepatitis related to the HBV infection or with liver failure during their participation in the study.
timeFrame: After 31 months from study entry
measure: Percentage of patients in which chemotherapy is delayed due to HBV-reactivation.
timeFrame: After 31 months from study entry
measure: Number of patients with DLBCL and with Chronic Lymphoid Leukemia who survive
timeFrame: After 31 months from study entry
measure: Number of patients experiencing adverse events.
timeFrame: After 31 months from study entry
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
city: Ancona
country: Italy
facility: Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica
city: Ascoli Piceno
country: Italy
facility: Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
city: Aviano
country: Italy
facility: Irccs Centro Di Riferimento Oncologico Di Aviano - Sosd Oncoematologia Trapianti Emopoietici E Terapie Cellulari
city: Bari
country: Italy
facility: Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
city: Bari
country: Italy
facility: Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia
city: Brindisi
country: Italy
facility: Asl Brindisi, Ospedale 'Perrino' - Brindisi - Uo Ematologia
city: Catania
country: Italy
facility: Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania
city: Cona
country: Italy
facility: Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
city: Foggia
country: Italy
facility: Aou Ospedali Riuniti - Foggia - Uoc Ematologia
city: Lecce
country: Italy
facility: Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia
city: Messina
country: Italy
facility: Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia
city: Napoli
country: Italy
facility: Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo
city: Napoli
country: Italy
facility: Aou Federico Ii - Napoli - Uoc Ematologia
city: Novara
country: Italy
facility: Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
city: Pagani
country: Italy
facility: Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
city: Palermo
country: Italy
facility: Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
city: Pavia
country: Italy
facility: Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
city: Pescara
country: Italy
facility: Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica
city: Reggio Emilia
country: Italy
facility: Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
city: Rimini
country: Italy
facility: Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
city: Roma
country: Italy
facility: Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali
city: Roma
country: Italy
facility: Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
city: Roma
country: Italy
facility: Aou Sant'Andrea - Roma - Uoc Ematologia
city: Roma
country: Italy
facility: Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: San Giovanni Rotondo
country: Italy
facility: Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino
city: Verona
country: Italy
facility: Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia
city: Vicenza
country: Italy
facility: Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia
Study officials:
affiliation: Università Sapienza di Roma
name: Giuseppe Gentile
role: STUDY_CHAIR
affiliation: Università Sapienza di Roma
name: Alessandra Micozzi
role: STUDY_DIRECTOR
References:
citation: Picardi M, Giordano C, Della Pepa R, Pugliese N, Leone A, Delle Cave G, Iula R, Pane F, Gentile G. Regarding "Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor in Diffuse Large B-Cell Lymphoma in the Rituximab Era". Oncologist. 2021 Jun;26(6):e1083-e1084. doi: 10.1002/onco.13710. Epub 2021 Feb 24.