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

NCT00931229 | Unknown DMC

• 1 other identifier: T1408
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Hodgkin's Lymphoma

Keywords

hepatitis B reactivation

Outcome Measures

Primary Outcomes (1)

• enroll 150 patients

  3 years

Study Arms (1)

entecavir

EXPERIMENTAL

All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines.

Drug: entecavir

Interventions

entecavir DRUG

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.

entecavir

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Evidence of 'resolved' HBV infection. Eligible subjects must be negative for serum HBV surface antigen (HBsAg) and positive for anti-core antibody (anti-HBc).
• Age \>18 years.
• Performance status with ECOG score 0-2.
• No previous chemotherapy and radiotherapy, no concurrent glucocorticoid use.
• Absolute neutrophil count (ANC) \> 1,500/mm3, platelet \> 100,000/mm3 in the peripheral blood.
• Total bilirubin \< 2.5 mg/dl. Alanine aminotransferase (ALT) \< 3 times UNL (upper limits of normal range).
• Serum creatinine \< 1.5 mg/dl. 9.10.Life expectancy 3 months.
• Signed informed consent.

You may not qualify if:

• Pregnant or breast-feeding women.
• Patients with history of brain metastasis or CNS involvement.
• Child's class B or C in patients with liver cirrhosis.
• Impaired cardiac function with NYHA (New York Heart Association) classification Gr II.
• History of other liver diseases such as hepatitis C, D, autoimmune hepatitis, primary biliary cirrhosis, Wilsons' disease.
• Other major systemic disease, such as active infection, significant cardiac disease, neurological deficit or psychiatric disorder, that the investigators consider to be significant risk.
• Any concomitant cancer treatment.
• Known hypersensitivity of any of the study drugs (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).
• Known human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Taiwan University Hospital: collaborator
• Mackay Memorial Hospital: collaborator
• China Medical University Hospital: collaborator
• Chi Mei Medical Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• Kaohsiung Veterans General Hospital.: collaborator
• Kaohsiung Medical University: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

entecavir

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Tsang-Wu Liu, Ph.D

  National Health Research Institutes, Taiwan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: July 2, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 9, 2016

Record last verified: 2011-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)