Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
Bristol-Myers Squibb
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital, Taiwan

Tracking Information
First Submitted Date  ICMJE June 22, 2009
First Posted Date  ICMJE June 24, 2009
Last Update Posted Date May 29, 2013
Study Start Date  ICMJE April 2009
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2013)
The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy. [ Time Frame: monthly, till 12 months after chemotherapy ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2009)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prophylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B
Official Title  ICMJE Prophylactic Use of Entecavir for Chemotherapy Associated With Hepatitis B Reactivation in HBsAg (-), Anti-HBc (+) Non-Hodgkin's Lymphoma Patients: a Randomized Controlled Trial
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Non Hodgkin's Lymphoma
  • Hepatitis B
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2013)
80
Original Estimated Enrollment  ICMJE
 (submitted: June 23, 2009)
90
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00926757
Other Study ID Numbers  ICMJE VGHUST98-P1-07
VGHIRB98-01-08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party vghtpe user, Taipei Veterans General Hospital, Taiwan
Study Sponsor  ICMJE Taipei Veterans General Hospital, Taiwan
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Yi-Hsiang Huang, MD, PhD Taipei Veterans General Hospital, Taiwan
PRS Account Taipei Veterans General Hospital, Taiwan
Verification Date May 2013

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