Prophylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B

Hepatitis B Clinical Trial

— HBVNHL  

Official title:

Prophylactic Use of Entecavir for Chemotherapy Associated With Hepatitis B Reactivation in HBsAg (-), Anti-HBc (+) Non-Hodgkin's Lymphoma Patients: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00926757
• Other study ID #: VGHUST98-P1-07
• Secondary ID: VGHIRB98-01-08
• Status: Completed
• Phase: Phase 4
• First received: June 22, 2009
• Last updated: May 27, 2013
• Start date: April 2009
• Est. completion date: November 2012

Study information

• Verified date: May 2013
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Hepatitis B (HBV) reactivation and hepatitis flare induced by cytotoxic chemotherapy is common in cancer patients who have chronic HBV infection. Lymphoma patients who had previous infected by HBV but negative for HBsAg have a the risk of HBV reactivation during chemotherapy, but prophylactic antiviral treatment is not a routine by current American Association for the Study of Liver Diseases (AASLD) guideline. Prophylactic entecavir might reduce the risk of HBV reactivation in such patients.

Description:

Hepatitis B (HBV) reactivation and hepatitis flare induced by cytotoxic chemotherapy is common in cancer patients who have chronic HBV infection. It is best characterized in patients with hematological malignancies such as non-Hodgkin's lymphoma but also can occur in patients with solid tumors. Reactivation during the initiation of chemotherapy may cause delay in cancer treatment and decrease in overall survival. The direct mortality caused by HBV reactivation, predominantly acute liver failure, ranges from 4% to 60%. Based on currently available information, it is well documented that HBV carriers should receive antiviral agents to prevent hepatitis B flare before receiving immunosuppressive agents and chemotherapy. However, development of hepatitis, acute liver failure, and mortality can occur among patients who are HBsAg negative but anti-HBc positive at the time of chemotherapy. Therefore, before the initiation of cytotoxic chemotherapy in cases of non-Hodgkin's lymphoma, it is unknown whether patients previous infected by HBV but negative HBsAg should routinely receive antiviral agents for prevention of HBV flare. In addition, the major concern of long-term lamivudine use is the selection of drug-resistant mutations. Based on these, we designed this current study to address the above important issues. Eligible patients are newly diagnosed, histologically proven anti-CD20-positive non-Hodgkin's lymphoma at our hospital. Patients should be negative of HBsAg but positive of serum anti-HBc. After signing the patient consent form, serum samples will be stored for further genotyping and quantitative HBV DNA testing. Patients will be randomized into two groups. In the prophylactic use group, participants will initiate entecavir 0.5 mg/day orally on day 1 of the first course of chemotherapy. Entecavir treatment will be continued until 3 months after the completion of chemotherapy and achieving the remission of the hepatitis (ALT normalization and undetectable HBV DNA). In the therapeutic use group, patients will start entecavir therapy, 0.5 mg/day orally, only when elevation of ALT (>100 U/L) and HBV DNA (>2000 IU/ml) developed during follow-up, or in the situation of HBsAg reverse seroconversion, and continued entecavir treatment until hepatitis resolved. The primary endpoint is the incidence of HBV reactivation during and within 12 months after completing chemotherapy in diffuse large B cell or follicular lymphoma patients who receive R-CHOP regimen. The secondary endpoint is the incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• CD20 positive lymphoma

• negative for HBsAg and positive for anti-HBc

• age over 16 years old

• alanine aminotransferase less than 2 times the upper limit of normal

• bilirubin < 2.5 mg/dL

• neutrophil > 2000/mm3

• platelet > 100,000/mm3

• creatinine < 1.5 mg/dL

• urea nitrogen < 25 mg/dL

• Eastern Cooperative Oncology Group performance score 0 to 2

Exclusion Criteria:

• Child-Pugh class B or C cirrhosis

• grade 2 or greater heart failure by the NYHA classification

• previous chemotherapy,radiotherapy, or concurrent glucocorticoid therapy for other reasons

• other primary liver diseases, such as chronic hepatitis C, hepatitis D, autoimmune hepatitis, or Wilsons' disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin's Lymphoma

Intervention

Drug:
• Entecavir prophylaxis
Entecavir 0.5mg daily from day 1 of chemotherapy to 3 months after completing chemotherapy
• Therapeutic entecavir
Entecavir 0.5cm daily since hepatitis flare and HBV reactivation, till hepatitis remission

Locations

Country	Name	City	State
Taiwan	Taipei Veterans General Hospital-Division of Gastroenterology, Division of Oncology	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan	Bristol-Myers Squibb

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the incidence of HBV reactivation during and within 12 months after chemotherapy		Monthly, and till 12 months after chemotherapy	Yes
Secondary	The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy.		monthly, till 12 months after chemotherapy	Yes