Non Hodgkin's LymphomaPhase 4HBVNHLNCT00926757
Prophylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B
A Phase 4 study testing Entecavir prophylaxis and Therapeutic entecavir in people with Non Hodgkin's Lymphoma and Hepatitis B, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Non Hodgkin's Lymphoma, Hepatitis B
- What is being tested?
- Entecavir prophylaxis and Therapeutic entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2009to Nov 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- platelet > 100,000/mm3
- creatinine < 1.5 mg/dL
- urea nitrogen < 25 mg/dL
- Eastern Cooperative Oncology Group performance score 0 to 2
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Taipei Veterans General Hospital-Division of Gastroenterology, Division of Oncology
Taipei, 11217
About this study
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
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.
Read the 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.
- Conditions
- Non Hodgkin's Lymphoma, Hepatitis B
- Being tested
- Entecavir prophylaxis, Therapeutic entecavir
- Keywords
- lymphoma, CD20, Hepatitis B virus, reactivation, Rituximab
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hepatitis B, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Entecavir prophylaxisDrug
Also called Baraclude
Entecavir 0.5mg daily from day 1 of chemotherapy to 3 months after completing chemotherapy
Therapeutic entecavirDrug
Also called Baraclude
Entecavir 0.5cm daily since hepatitis flare and HBV reactivation, till hepatitis remission
| Study group | Role | What they receive |
|---|---|---|
| Entecavir prophylaxis | Experimental | 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. Receives: Drug: Entecavir prophylaxis |
| Therapeutic arm | Active comparator | In patients with HBV reactivation and ALT flare > 100 U/L, entecavir 0.5mg daily will be prescribed for the cases till hepatitis remission Receives: Drug: Therapeutic entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the incidence of HBV reactivation during and within 12 months after chemotherapy
Measured: Monthly, and till 12 months after chemotherapy
Secondary outcomes (1)
The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy.
Measured: monthly, till 12 months after chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2009 (estimated)
- Study startApr 2009
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
- Investigators
- Yi-Hsiang Huang, MD, PhD, Principal investigator, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00926757
- Sponsor's protocol ID
- VGHUST98-P1-07
- Other IDs
- VGHIRB98-01-08
- Acronym
- HBVNHL
- Status last verified
- May 2013
- First submitted
- 22 Jun 2009
- Last updated
- 29 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 23775967
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00926757
- Acronym / sponsor ID
- HBVNHL / VGHUST98-P1-07
- Conditions
- Non Hodgkin's Lymphoma, Hepatitis B
- Keywords
- lymphoma, CD20, Hepatitis B virus, reactivation, Rituximab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Collaborators
- Bristol-Myers Squibb
- Study start
- Apr 2009
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 24 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entecavir prophylaxis | Experimental | Drug: Entecavir prophylaxisParticipants 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. |
| Therapeutic arm | Active comparator | Drug: Therapeutic entecavirIn patients with HBV reactivation and ALT flare > 100 U/L, entecavir 0.5mg daily will be prescribed for the cases till hepatitis remission |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Entecavir prophylaxisAlso: BaracludeEntecavir 0.5mg daily from day 1 of chemotherapy to 3 months after completing chemotherapy | Drug | Entecavir prophylaxis |
| Therapeutic entecavirAlso: BaracludeEntecavir 0.5cm daily since hepatitis flare and HBV reactivation, till hepatitis remission | Drug | Therapeutic arm |
Primary outcome
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
1 secondary outcome
The incidence of HBsAg reverse seroconversion during and within 12 months after completing chemotherapy.
Time frame: monthly, till 12 months after chemotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2013.
- Derived from this study: PubMed 23775967Huang 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.
Related trials for Non Hodgkin's Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Hsiang Huang, MD, PhD principal investigator
Taipei Veterans General Hospital, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entecavir prophylaxis and Therapeutic entecavir in people with Non Hodgkin's Lymphoma and Hepatitis B, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00926757, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2013.