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

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 All subjects will receive TAF 1-3 weeks before Rituximab+Chemotherapy and withdrawn 12 months after the completion of chemotherapy.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

Official Title
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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

Conditions
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Large-B-cell Diffuse Lymphoma, Chronic Lymphoid Leukemia

Intervention / Treatment
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* Drug: Rituximab
* Drug: Chemotherapy
* Drug: Tenofovir alafenamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>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<br>* 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.<br>Drug: Chemotherapy<br>* 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.<br>Drug: Tenofovir alafenamide<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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. | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diffuse Large B-Cell Lymphoma, chronic Lymphoid Leukemia HBsAg-positive, Rituximab, chemotherapy, alafenamide, hepatitis B virus reactivation