Incidence of Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients
Status:
Unknown status
Trial end date:
2017-12-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
N/A
Details
Lead Sponsor:
National Health Research Institutes, Taiwan
Collaborators:
Chi Mei Medical Hospital China Medical University Hospital Kaohsiung Medical University Kaohsiung Veterans General Hospital. Mackay Memorial Hospital National Taiwan University Hospital Taichung Veterans General Hospital