The Incidence of Hepatitis B in Diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive Treated With Rituximab, Chemotherapy and Tenofovir Alafenamide

Chronic Lymphoid Leukemia Clinical Trial

— CLL1818  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03804372
• Other study ID #: CLL1818
• Status: Recruiting
• Phase: Phase 2
• Start date: July 7, 2020
• Est. completion date: July 2024

Study information

• Verified date: January 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: +39 0670390514
• Email: p.fazi[@]gimema.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 All subjects will receive TAF 1-3 weeks before Rituximab+Chemotherapy and withdrawn 12 months after the completion of chemotherapy.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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: July 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphoid Leukemia
• Hepatitis
• Hepatitis B
• Large-B-cell Diffuse Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Rituximab
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.
• Chemotherapy
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.
• Tenofovir alafenamide
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.

Locations

Country	Name	City	State
Italy	Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia	Alessandria
Italy	Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica	Ancona
Italy	Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia	Ascoli Piceno
Italy	Irccs Centro Di Riferimento Oncologico Di Aviano - Sosd Oncoematologia Trapianti Emopoietici E Terapie Cellulari	Aviano
Italy	Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto	Bari
Italy	Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia	Bari
Italy	Asl Brindisi, Ospedale 'Perrino' - Brindisi - Uo Ematologia	Brindisi
Italy	Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania	Catania
Italy	Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione	Cona
Italy	Aou Ospedali Riuniti - Foggia - Uoc Ematologia	Foggia
Italy	Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia	Lecce
Italy	Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia	Messina
Italy	Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo	Napoli
Italy	Aou Federico Ii - Napoli - Uoc Ematologia	Napoli
Italy	Aou Maggiore Della Carita' Di Novara - Scdu Ematologia	Novara
Italy	Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia	Pagani
Italy	Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo	Palermo
Italy	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia
Italy	Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica	Pescara
Italy	Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia	Reggio Emilia
Italy	Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia	Rimini
Italy	Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali	Roma
Italy	Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali	Roma
Italy	Aou Sant'Andrea - Roma - Uoc Ematologia	Roma
Italy	Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica	Roma
Italy	Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia	Roma	(rm)
Italy	Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia	San Giovanni Rotondo
Italy	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino	Torino
Italy	Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia	Verona
Italy	Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients presenting hepatitis B virus reactivation	Assessment of the percentage of patients presenting HBV reactivation within 6 months following the start of treatment with Rituximab, chemotherapy and TAF in in DLBCL and Chronic Lymphoid Leukemia patients.	Within 6 months following the start of treatment
Secondary	Percentage of patients presenting hepatitis B virus reactivation	Assessment of the percentage of patients presenting HBV reactivation during and after the 12-month treatment of TAF as a single agent in in DLBCL and Chronic Lymphoid Leukemia patients	After 12 months following the study entry and start of treatment
Secondary	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.		After 31 months from study entry
Secondary	Percentage of patients in which chemotherapy is delayed due to HBV-reactivation.	In terms of percentage of patients with a delay of at least 7 days between chemotherapy cycles stratified by DLBCL and chronic lymphoid leukemia.	After 31 months from study entry
Secondary	Number of patients with DLBCL and with Chronic Lymphoid Leukemia who survive		After 31 months from study entry
Secondary	Number of patients experiencing adverse events.		After 31 months from study entry