Factors Influencing Hepatitis B Virus Reactivation in Lymphoma Patients Treated With Rituximab

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Won Seog Kim, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01311232
First received: March 6, 2011
Last updated: January 12, 2013
Last verified: January 2013
  Purpose

This study is a retrospective analysis to identify factors influencing hepatitis B virus reactivation in patients treated with rituximab containing chemotherapy. Rituximab monoclonal antibody targeting CD20 induces B-cell depletion resulting in prolonged immune suppression. This leads to frequent reactivation of patients with a previous history of exposure to HBV or HBV carrier.

We collect the clinical features and laboratory findings of patients satisfied the inclusion criteria as follows.

  1. Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) or \ follicular B-cell lymphoma (FL).
  2. Patients who had received at least two cycles of rituximab-CHOP or rituximab-CVP as a primary treatment
  3. Patients with a history of previous exposure to HBV

    • HBV surface antigen (HBs Ag) positive Or
    • HBV core antibody (IgG anti-HBc antibody) positive

Then, we compare the HBV reactivation group with the control group (HBV reactivation does not happen) to find factors influencing HBV reactivation.


Condition
Patients With Diffuse Large B-cell Lymphoma or Follicular Lymphoma
Patients Treated With Rituximab-CHOP or Rituximab-CVP

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Hepatitis B Virus Reactivation in Asian Patients Treated With Rituximab-containing Treatment

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Hepatitis B virus reactivation [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: November 2010
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Case
Patients with HBV reactivation
Control
Patients without HBV reactivation

Detailed Description:

Description of factors associated with Hepatitis B virus reactivation:

  • Laboratory parameters defining HBV status/activity at time of treatment initiation
  • Lymphoma stage at rituximab treatment initiation (Ann Arbor, B-symptoms, bone marrow involvement, IPI, ECOG-score, LDH)
  • Immunochemotherapy regimen (treatment line, rituximab dose and cycle)
  • Disease status at time of HBV reactivation
  • Antiviral prophylaxis (medication, dose, duration at time at time of reactivation)
  • Patient demographics (age, gender, residence, ethnic origin, smoking status, alcohol consumption and occupation)

Time to Hepatitis B virus reactivation

  • The time from start of rituximab-containing immunochemotherapy until first evidence of HBV reactivation meeting the criteria
  • Description of prophylaxis and treatment with antiviral medication HBV vaccination Time of initiation of antiviral therapy of prophylaxis relating to clinical or laboratory signs of possible HBV reactivation Anti-viral medication used in prophylaxis or therapy
  • Description of outcomes Outcomes of the HBV reactivation Outcomes of the rituximab-containing immunochemotherapy Demographics and previous infection history: Age, gender, nationality, race, social history, past medical history
  • Parameters associated with lymphomas: Ann Arbor stage, number of extranodal involvement, serum LDH, serum β2-microglobulin, ECOG performance status, presence of B symptoms, International Prognostic Index, bone marrow invasion
  • Laboratory parameters associated with hepatitis B virus:

hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti- HBs), hepatitis B e antigen (HBeAg), hepatitis B core antibody (anti-HBc), hepatitis B e antibody (anti-HBe), serum HBV DNA

  • Lymphoma treatment history:

Line of treatment (first line, second line), rituximab and chemotherapy administration (dose, schedule), start date, last treatment date

  • Prophylaxis or treatment against HBV reactivation:

antiviral drug (dose, schedule, duration)

  • Hepatitis B virus reactivation:

onset, serologic markers, outcome

  Eligibility

Ages Eligible for Study:   15 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with hepatitis B virus positivity and treated with rituximab-containing chemotherapy to treat their disease, diffuse large B-cell lymphoma or follicular lymphoma

Criteria

Inclusion Criteria

  1. Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) or follicular B-cell lymphoma (FL).
  2. Patients who had received at least two cycles of rituximab-CHOP or rituximab-CVP as a primary treatment
  3. Patients with a history of previous exposure to HBV

    • HBV surface antigen (HBs Ag) positive Or
    • HBV core antibody (IgG anti-HBc antibody) positive
  4. Patients with documented HBV reactivation (definite or presumptive) occurring during treatment (at least two cycles of R-CHOP or R-CVP) or within 12 months after the last dose of rituximab

    • Definitive HBV reactivation

      - Elevation of serum HBV DNA level >1 log IU/mL from baseline or absolute increase of HBV DNA by 6 log10 IU/mL in HBsAg positive patients

    • Presumptive HBV reactivation - Increase of ALT (≥3x baseline value or absolute value of ≥100 U/L) and positive conversion of HBs Ag in previously HBsAg-negative patients

Exclusion Criteria:

  1. Patients who had received chemotherapy other than R-CHOP or R-CVP after diagnosis
  2. patients diagnosed with HIV, HCV or HDV co-infection
  3. Patients who had undergone allogenic stem cell transplantation before hepatitis B virus reactivation was documented
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01311232

Locations
China
Queen Mary Hospital
Hing Kong, China
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Malaysia
Hospital Kuala Lumpur
Kuala Lumpur, Malaysia
Singapore
National Cancer Center
Singapore, Singapore
Sponsors and Collaborators
Samsung Medical Center
  More Information

No publications provided

Responsible Party: Won Seog Kim, Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01311232     History of Changes
Other Study ID Numbers: 2010-11-035
Study First Received: March 6, 2011
Last Updated: January 12, 2013
Health Authority: Korea: Ministry for Health, Welfare and Family Affairs

Keywords provided by Samsung Medical Center:
rituximab, lymphoma, hepatitis B virus

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014