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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00926757
Recruitment Status : Completed
First Posted : June 24, 2009
Last Update Posted : May 29, 2013
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Non Hodgkin's Lymphoma Hepatitis B Drug: Entecavir prophylaxis Drug: Therapeutic entecavir Phase 4

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
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
Study Start Date : April 2009
Primary Completion Date : November 2012
Study Completion Date : November 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir
U.S. FDA Resources

Arms and Interventions

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 Name: 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 Name: Baraclude


Outcome Measures

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy. [ Time Frame: monthly, till 12 months after chemotherapy ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00926757


Locations
Taiwan
Taipei Veterans General Hospital-Division of Gastroenterology, Division of Oncology
Taipei, Taiwan, 11217
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Bristol-Myers Squibb
Investigators
Principal Investigator: Yi-Hsiang Huang, MD, PhD Taipei Veterans General Hospital, Taiwan
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: vghtpe user, Yi-Hsiang Huang, Professor, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier: NCT00926757     History of Changes
Other Study ID Numbers: VGHUST98-P1-07
VGHIRB98-01-08
First Posted: June 24, 2009    Key Record Dates
Last Update Posted: May 29, 2013
Last Verified: May 2013

Keywords provided by vghtpe user, Taipei Veterans General Hospital,Taiwan:
lymphoma
CD20
Hepatitis B virus
reactivation
Rituximab

Additional relevant MeSH terms:
Lymphoma
Hepatitis
Hepatitis A
Lymphoma, Non-Hodgkin
Hepatitis B
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents