Safety & Efficacy of Lamivudine & Tenofovir to Lower Plasma Level of Viral RNA in Lymphoma
Status:
Withdrawn
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Therapy for non-Hodgkin lymphoma (NHL) is in evolution as new molecular pathways and targeted
therapies are identified. Although most NHLs respond to currently available therapies, the
majority of patients relapse and many never have a complete response to therapy. In the
investigators attempts to further understand the pathogenesis of NHLs, the investigators have
identified and characterized expression of human endogenous retroviruses (HERVs) at the DNA,
RNA and protein levels in association with the presence of NHLs (and other neoplastic
diseases). The investigators preclinical evidence suggests a correlation with the level of
HERV-K (a particular family of HERVs) expression and NHL disease activity, leading us to
hypothesize that HERV-K expression may contribute to the development of the disease and/or to
its recurrence. If this hypothesis is correct, then drugs that inhibit HERV-K expression may
prevent recurrence of disease and/or may provide a novel therapeutic approach for NHLs.
To test this hypothesis, the investigators eventually intend to study the use of
anti-retroviral therapies in patients with NHL. The investigators in vitro studies have
demonstrated that HERV-K expression decreases in response to the currently FDA-approved and
available, anti-HIV drugs, Lamivudine and tenofovir disoproxil fumarate (tenofovir). These
medications are tolerated well in HIV patients, but it is unknown how the combination of
Lamivudine and Tenofovir will be tolerated by patients with NHL. To further test the
investigators hypotheses, the investigators propose the following Specific Aims of the
current study: (1) To evaluate the tolerability, toxicity and safety of administering
Lamivudine and Tenofovir in combination to patients with relapsed or refractory NHL; (2) To
evaluate the effects of the combination of lamivudine and tenofovir on HERV-K plasma viral
RNA load; and (3) To monitor the response rate of the NHL to treatment with the combination
of lamivudine and tenofovir.
The investigators study will recruit adult patients with relapsed or refractory NHL whom the
investigators have identified as having expression of HERV-K. Volunteer participants will be
administered the combination of lamivudine and tenofovir and monitored for tolerability,
toxicity, compliance, changes in viral RNA load and disease response.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
University of Michigan Cancer Center University of Michigan Rogel Cancer Center