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

May 27, 2013 updated by: vghtpe user, Taipei Veterans General Hospital, Taiwan

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital-Division of Gastroenterology, Division of Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Entecavir prophylaxis
Participants will initiate entecavir 0.5 mg/day orally on day 1 of the first course of chemotherapy, and will be continued until 3 months after completion of the chemotherapy.
Drug: Entecavir prophylaxis
Entecavir 0.5mg daily from day 1 of chemotherapy to 3 months after completing chemotherapy
Other Names:
  • Baraclude
ACTIVE_COMPARATOR: Therapeutic arm
In patients with HBV reactivation and ALT flare > 100 U/L, entecavir 0.5mg daily will be prescribed for the cases till hepatitis remission
Drug: Therapeutic entecavir
Entecavir 0.5cm daily since hepatitis flare and HBV reactivation, till hepatitis remission
Other Names:
  • Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint is the incidence of HBV reactivation during and within 12 months after chemotherapy
Time Frame: Monthly, and till 12 months after chemotherapy
Monthly, and till 12 months after chemotherapy

Secondary Outcome Measures

Outcome Measure
Time Frame
The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy.
Time Frame: monthly, till 12 months after chemotherapy
monthly, till 12 months after chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Yi-Hsiang Huang, MD, PhD, Taipei Veterans General Hospital, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (ACTUAL)

November 1, 2012

Study Completion (ACTUAL)

November 1, 2012

Study Registration Dates

First Submitted

June 22, 2009

First Submitted That Met QC Criteria

June 23, 2009

First Posted (ESTIMATE)

June 24, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

May 29, 2013

Last Update Submitted That Met QC Criteria

May 27, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VGHUST98-P1-07
  • VGHIRB98-01-08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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