CLL1818: The Incidence of Hepatitis B in Diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive Treated With Rituximab, Chemotherapy and Tenofovir Alafenamide

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

Overall Status

Recruiting

CT.gov ID

NCT03804372

Collaborator

(none)

180

Enrollment

Locations

Arm

47.8

Anticipated Duration (Months)

5.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Large-B-cell Diffuse Lymphoma Chronic Lymphoid Leukemia	Drug: Rituximab Drug: Chemotherapy Drug: Tenofovir alafenamide	Phase 2

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 All subjects will receive TAF 1-3 weeks before Rituximab+Chemotherapy and withdrawn 12 months after the completion of chemotherapy.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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 7, 2020

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study group 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.	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. Drug: 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. Drug: 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.

Arm

Intervention/Treatment

Experimental: Study group

Drug: Rituximab

Drug: Chemotherapy

Drug: Tenofovir alafenamide

Outcome Measures

Primary Outcome Measures

Percentage of patients presenting hepatitis B virus reactivation [Within 6 months following the start of treatment]
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.

Secondary Outcome Measures

Percentage of patients presenting hepatitis B virus reactivation [After 12 months following the study entry and start of treatment]
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
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]
Percentage of patients in which chemotherapy is delayed due to HBV-reactivation. [After 31 months from study entry]
In terms of percentage of patients with a delay of at least 7 days between chemotherapy cycles stratified by DLBCL and chronic lymphoid leukemia.
Number of patients with DLBCL and with Chronic Lymphoid Leukemia who survive [After 31 months from study entry]
Number of patients experiencing adverse events. [After 31 months from study entry]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country
1	Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia	Roma	(rm)	Italy
2	Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia	Alessandria		Italy
3	Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica	Ancona		Italy
4	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
5	Irccs Centro Di Riferimento Oncologico Di Aviano - Sosd Oncoematologia Trapianti Emopoietici E Terapie Cellulari	Aviano		Italy
6	Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto	Bari		Italy
7	Irccs Oncologico Istituto Tumori Giovanni Paolo Ii - Bari - Uo Ematologia	Bari		Italy
8	Asl Brindisi, Ospedale 'Perrino' - Brindisi - Uo Ematologia	Brindisi		Italy
9	Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania	Catania		Italy
10	Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione	Cona		Italy
11	Aou Ospedali Riuniti - Foggia - Uoc Ematologia	Foggia		Italy
12	Asl Lecce, Ospedale 'V. Fazzi' - Uo Ematologia	Lecce		Italy
13	Ao Ospedali Riuniti "Papardo Piemonte" - Po Papardo - Messina - Sc Ematologia	Messina		Italy
14	Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo	Napoli		Italy
15	Aou Federico Ii - Napoli - Uoc Ematologia	Napoli		Italy
16	Aou Maggiore Della Carita' Di Novara - Scdu Ematologia	Novara		Italy
17	Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia	Pagani		Italy
18	Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo	Palermo		Italy
19	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia		Italy
20	Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica	Pescara		Italy
21	Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia	Reggio Emilia		Italy
22	Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia	Rimini		Italy
23	Ao San Camillo Forlanini - Roma - Uoc Ematologia E Trapianto Cellule Staminali	Roma		Italy
24	Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali	Roma		Italy
25	Aou Sant'Andrea - Roma - Uoc Ematologia	Roma		Italy
26	Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia	Roma		Italy
27	Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica	Roma		Italy
28	Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia	San Giovanni Rotondo		Italy
29	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino	Torino		Italy
30	Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia	Verona		Italy
31	Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia	Vicenza		Italy