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Incidence of Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Taiwan University Hospital
Mackay Memorial Hospital
China Medical University Hospital
Chi Mei Medical Hospital
Taichung Veterans General Hospital
Kaohsiung Veterans General Hospital.
Kaohsiung Medical University
Information provided by (Responsible Party):
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT00931229
First received: June 29, 2009
Last updated: November 8, 2016
Last verified: December 2011
  Purpose

This is a single-arm study. Key eligibility criteria include (1) newly diagnosed, diffuse large B-cell or follicular cell non-Hodgkin's lymphoma; (2) negative test for hepatitis B surface antigen (HBsAg) and positive for antibody to hepatitis B core antigen (anti-HBc); (3) adequate bone marrow, liver, and kidney function. All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines. The primary endpoint of this study is the incidence of hepatitis B virus (HBV) reactivation, defined by a greater than 10-fold increase, compared with previous nadir levels, of HBV DNA during rituximab-CHOP chemotherapy and within 1 year after completion of the last course of rituximab-CHOP chemotherapy. Patients who have HBV reactivation during the study period will receive free entecavir treatment, one of the standard treatment for chronic hepatitis B, for 48 weeks. The secondary endpoints include the incidence of hepatitis flare, defined as a greater than 3 fold increase of serum alanine aminotransferase (ALT) level that exceeded 100 IU/L, and the efficacy and safety of rituximab-CHOP chemotherapy.

In the T1408 study we enrolled patients with newly diagnosed lymphoma who were HBsAg (-) and anti-HBc (+) and were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy. Key findings of this study included (1) HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels, occurred to 10-20% of patients, depending on the sensitivity of the HBV DNA tests; (2) no HBV-related death with the prompt anti-viral therapy upon HBV reactivation; (3) patients with HBV reactivation were associated with poorer progression-free survival and overall survival; (4) serological breakthrough (i.e., re-appearance of HBsAg) is an important predictor of HBV-related hepatitis flare.

In this amendment we will enroll more patients to clarify the above findings: (1) the association between HBV reactivation and survival; (2) diagnostic value of quantitative HBsAg and anti HBc tests on HBV reactivation; (3) whether host factors (DNA polymorphism) may help predict HBV reactivation. A larger patient cohort is needed to identify (1) baseline features that may help predict HBV reactivation, and (2) on-treatment features that may help timely anti-viral therapy.


Condition Intervention
Non-Hodgkin's Lymphoma
Drug: entecavir

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Incidence of Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients Who Receive Rituximab-containing Chemotherapy and Are Previously Infected With Hepatitis B Virus

Resource links provided by NLM:


Further study details as provided by National Health Research Institutes, Taiwan:

Primary Outcome Measures:
  • enroll 150 patients [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 202
Study Start Date: June 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: entecavir
All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines.
Drug: entecavir
All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines. The primary endpoint of this study is the incidence of HBV reactivation, defined by a greater than 10-fold increase, compared with previous nadir levels, of HBV DNA during rituximab-CHOP chemotherapy and within 1 year after completion of the last course of rituximab-CHOP chemotherapy. Patients who have HBV reactivation during the study period will receive free entecavir treatment, one of the standard treatment for chronic hepatitis B, for 48 weeks.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven diffuse large B-cell or follicular B-cell non-Hodgkin's lymphoma, for which chemotherapy with rituximab-CHOP chemotherapy is considered treatment-of-choice.
  2. Evidence of 'resolved' HBV infection. Eligible subjects must be negative for serum HBV surface antigen (HBsAg) and positive for anti-core antibody (anti-HBc).
  3. Age >18 years.
  4. Performance status with ECOG score 0-2.
  5. No previous chemotherapy and radiotherapy, no concurrent glucocorticoid use.
  6. Absolute neutrophil count (ANC) > 1,500/mm3, platelet > 100,000/mm3 in the peripheral blood.
  7. Total bilirubin < 2.5 mg/dl. Alanine aminotransferase (ALT) < 3 times UNL (upper limits of normal range).
  8. Serum creatinine < 1.5 mg/dl. 9.10.Life expectancy 3 months.

11.Signed informed consent.

Exclusion Criteria:

  1. Pregnant or breast-feeding women.
  2. Patients with history of brain metastasis or CNS involvement.
  3. Child's class B or C in patients with liver cirrhosis.
  4. Impaired cardiac function with NYHA (New York Heart Association) classification Gr II.
  5. History of other liver diseases such as hepatitis C, D, autoimmune hepatitis, primary biliary cirrhosis, Wilsons' disease.
  6. Other major systemic disease, such as active infection, significant cardiac disease, neurological deficit or psychiatric disorder, that the investigators consider to be significant risk.
  7. Any concomitant cancer treatment.
  8. Known hypersensitivity of any of the study drugs (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).
  9. Known human immunodeficiency virus (HIV) infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931229

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Taiwan University Hospital
Mackay Memorial Hospital
China Medical University Hospital
Chi Mei Medical Hospital
Taichung Veterans General Hospital
Kaohsiung Veterans General Hospital.
Kaohsiung Medical University
Investigators
Study Director: Tsang-Wu Liu, Ph.D National Health Research Institutes, Taiwan
  More Information

Responsible Party: National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier: NCT00931229     History of Changes
Other Study ID Numbers: T1408 
Study First Received: June 29, 2009
Last Updated: November 8, 2016
Health Authority: Taiwan: Department of Health
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by National Health Research Institutes, Taiwan:
hepatitis B reactivation

Additional relevant MeSH terms:
Lymphoma
Hepatitis
Lymphoma, Non-Hodgkin
Hepatitis B
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Rituximab
Entecavir
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 02, 2016