Assessing Antibody Responsiveness to Hepatitis B Vaccine in Aged Lymphoma Patients Undergoing Treatment With Rituximab

NCT00863187 | Unknown

• 1 other identifier: 3097
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: The ability of the immune system to function declines with aging. This is reflected by a marked decrease in the responsiveness to vaccinations and to infectious agents. Consequentially, there is a profound reduction in the quality of live and an increased dependency on the health systems. Studies have shown that the production of B lymphocytes in the bone marrow declines with aging and long-lived B cells accumulate in the periphery. Thus, instead of a juvenile repertoire of B cells that is capable to recognize any new pathogen, the repertoire of the elderly becomes more restricted and fails to respond to new antigens. Working hypothesis and aims: We hypothesize that the dramatic change in the cellular composition in aging reflects homeostasis pressures that are set by long-lived peripheral B cells. Here, the investigators hypothesize that altering the homeostasis, by active depletion of the peripheral B cells, will revive B lymphopoiesis in the BM and rejuvenate the peripheral repertoire of B cells in aging. Consequentially, this will significantly improve immune responsiveness of aged individuals to new antigenic challenges. Methods: The investigators propose a parallel study in human and mouse. For our clinical study we will use old lymphoma patients that were treated with the B cell depleting therapy, RITUXIMAB, for transient B cell depletion and established full B cell reconstitution. We will test the responsiveness of these patients to hepatitis B vaccine and compare it to aged-matched control group. The investigators will also use old human CD20 transgenic mice where B cell depletion is imposed by anti human CD20 antibodies. In these experiments we will study physiological and immunological changes to understand aging mechanisms in the B lineage. Expected results: We expect that old patients treated for B cell depletion will have an increased responsiveness to the hepatitis B vaccine relative to the control group. Importance: The investigators propose an efficient approach to improve immune response in the elderly population. This will increase efficacy of vaccination, reduce morbidity and improve quality of life. It will also reduce the cost of medical treatment. In addition, this study will show that senescence in the B lineage can be reversed, which is in contrast to the general concepts of aging. Probable implications to the welfare and health of the aged population Medicine: Improving the immune competence will increase efficacy of vaccination, reduce morbidity, and reduce dependency on health systems. This will significantly improve the quality of life.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• anti hepatitis B antibodies

  3 month

Secondary Outcomes (1)

• B cell proliferation and antibody secretion in response to stimulation in vitro

  3 month

Study Arms (1)

rituximab

EXPERIMENTAL

b cell depletion drug

Biological: rituximab

Interventions

rituximab BIOLOGICAL

b cell depletion

rituximab

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older
• lymphoma
• rituximab

You may not qualify if:

• disease remission

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Technion, Israel Institute of Technology: collaborator

Related Publications (1)

• Dowery R, Benhamou D, Benchetrit E, Harel O, Nevelsky A, Zisman-Rozen S, Braun-Moscovici Y, Balbir-Gurman A, Avivi I, Shechter A, Berdnik D, Wyss-Coray T, Melamed D. Peripheral B cells repress B-cell regeneration in aging through a TNF-alpha/IGFBP-1/IGF-1 immune-endocrine axis. Blood. 2021 Nov 11;138(19):1817-1829. doi: 10.1182/blood.2021012428.

  PMID: 34297797 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 15, 2009
• First Posted: March 17, 2009
• Study Start: February 1, 2009
• Primary Completion: February 1, 2010
• Last Updated: March 17, 2009

Record last verified: 2009-02