Safety & Efficacy of Lamivudine & Tenofovir to Lower Plasma Level of Viral RNA in Lymphoma
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.
Drug: Tenofovir disoproxil fumarate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase I/II Study of Safety and Efficacy of Lamivudine (EPIVIR®) and Tenofovir Disoproxil Fumarate (VIREAD®) Used to Lower the Plasma Level of Viral RNA of HERV-K(HML2) in Patients With Lymphoma|
- Efficacy (effect on human endogenous retrovirus-K(HML2)[HERV-K(HML2)] [ Time Frame: 2 years ] [ Designated as safety issue: No ]Patients will have HERV-K(HML2) viral load measured at baseline and post-treatment (quantifiable HERV-K(HML2) viral load is an eligibility criterion, and post-treatment loads below the limit of quantitation will be assigned a random value uniformly distributed between 0 and the limit of quantitation).
- tumor regression [ Time Frame: 2 years ] [ Designated as safety issue: No ]Linear models will be used to relate tumor regression to change in viral load of RNA levels.
- Toxicity will be tabulated according to NCI NCI Common Terminology Criteria for Adverse Events (CTCAE) v4 grade and classification [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2015|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Experimental: Study Drugs
The medications to be used in this study are Lamivudine (EPIVIR®) and Tenofovir disoproxil fumarate (VIREAD®), medications already used in people with certain other types of viruses [but not HERV-K(HML2)] in their body. Treatment will last 16 weeks. This is an experiment combining these two drugs and has been issue an Investigational New Drug (IND) Exemption by the FDA.
Creatinine Clearance (mL/min): ≥50, Recommended Dosage of Epivir: 150 mg twice daily or 300 mg once daily.
Creatinine Clearance (mL/min): 30-49, Recommended Dosage of Epivir: 150 mg once daily.
Subjects will be taking drug for 16 weeks.
Other Name: EpivirDrug: Tenofovir disoproxil fumarate
300 mg once a day p.o. for 16 weeks.
Other Name: Viread
Please refer to this study by its ClinicalTrials.gov identifier: NCT01528865
|Contact: Scott D Gitlin, MDemail@example.com|
|Contact: Cancer AnswerLinefirstname.lastname@example.org|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Scott D Gitlin, MD 734-936-5419|
|Principal Investigator: Scott D Gitlin, MD|