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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier:
NCT00926757
First received: June 22, 2009
Last updated: May 27, 2013
Last verified: May 2013

June 22, 2009
May 27, 2013
April 2009
November 2012   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00926757 on ClinicalTrials.gov Archive Site
The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy. [ Time Frame: monthly, till 12 months after chemotherapy ] [ Designated as safety issue: Yes ]
To evaluate the proportion of subjects in each group who discontinue study drug for clinical or laboratory adverse events. [ Time Frame: monthly, till 12 months after chemotherapy ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Prophylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
  • Non Hodgkin's Lymphoma
  • Hepatitis B
  • Drug: Entecavir prophylaxis
    Entecavir 0.5mg daily from day 1 of chemotherapy to 3 months after completing chemotherapy
    Other Name: Baraclude
  • Drug: Therapeutic entecavir
    Entecavir 0.5cm daily since hepatitis flare and HBV reactivation, till hepatitis remission
    Other Name: Baraclude
  • 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.
    Intervention: Drug: Entecavir prophylaxis
  • 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
    Intervention: Drug: Therapeutic entecavir
Huang YH, Hsiao LT, Hong YC, Chiou TJ, Yu YB, Gau JP, Liu CY, Yang MH, Tzeng CH, Lee PC, Lin HC, Lee SD. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013 Aug 1;31(22):2765-72. doi: 10.1200/JCO.2012.48.5938. Epub 2013 Jun 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
November 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT00926757
VGHUST98-P1-07, VGHIRB98-01-08
Yes
vghtpe user, Taipei Veterans General Hospital,Taiwan
Taipei Veterans General Hospital, Taiwan
Bristol-Myers Squibb
Principal Investigator: Yi-Hsiang Huang, MD, PhD Taipei Veterans General Hospital, Taiwan
Taipei Veterans General Hospital, Taiwan
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP