Safety & Efficacy of Lamivudine & Tenofovir to Lower Plasma Level of Viral RNA in Lymphoma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by University of Michigan Cancer Center
Sponsor:
Collaborators:
GlaxoSmithKline
Gilead Sciences
Information provided by (Responsible Party):
Scott Gitlin, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01528865
First received: January 12, 2012
Last updated: March 20, 2013
Last verified: March 2013

January 12, 2012
March 20, 2013
May 2013
August 2015   (final data collection date for primary outcome measure)
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).
Same as current
Complete list of historical versions of study NCT01528865 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity will be tabulated according to NCI CTCAE v4 grade and classification.
Same as current
Not Provided
Not Provided
 
Safety & Efficacy of Lamivudine & Tenofovir to Lower Plasma Level of Viral RNA in Lymphoma
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

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 fumarea (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.

Not Provided
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Lymphoma
  • Drug: Lamivudine

    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: Epivir
  • Drug: Tenofovir disoproxil fumarate
    300 mg once a day p.o. for 16 weeks.
    Other Name: Viread
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 IND Exemption by the FDA.
Interventions:
  • Drug: Lamivudine
  • Drug: Tenofovir disoproxil fumarate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
30
August 2016
August 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of non-Hodgkin lymphoma (NHL)
  • Must have HERV-K(HML2) viral load of ≥1x103 using a gag primer RT-PCR assay.
  • Must have bi-dimensionally measurable disease.
  • Patients with lymphomas that are felt to be incurable with any therapy and for whom there are no standard treatments that would be anticipated to be necessary or beneficial within the next 5 months. These patients can have received any amount of prior chemotherapy to enter this trial.
  • All previous therapies must have been discontinued at least 4 weeks prior to initiation of the administration of this study's drugs.
  • HIV negative by standard blood testing.
  • Have an expected life expectancy of at least 5 months.
  • Have an ECOG (Eastern Cooperative Oncology Group) performance scale status of 0 - 2l) Must have a serum creatinine <2.0 and creatinine clearance >30 ml/min/m2. Other organ dysfunction is eligible at the discretion of the PI.
  • Agree to use a reliable method of birth control prior to drug initiation and for the duration of their study participation.

Exclusion Criteria:

  • a) Have received chemotherapy or radiotherapy within 4 weeks
  • Have not recovered from the adverse effects or toxicities of lymphoma therapy most recently administered.
  • Currently receiving any other investigational medication or therapy.
  • Patients with a second malignancy that might interfere with interpretation of the results of this study.
  • Patients with known allergic reaction to lamivudine or tenofovir DF.
  • Patients on drugs that interfere with renal function or drugs that compete with tenofovir for active binding sites (i.e. intravenous cidofovir, acyclovir, ganciclovir, and valganciclovir).
  • Uncontrolled concurrent illnesses, including, but not limited to, active/ongoing infection, symptomatic congestive heart failure, unstable angina pectoris.
  • Women who are pregnant, become pregnant, or are breast-feeding.
  • Standard blood tests that are positive for HIV infection
Both
18 Years and older
No
Contact: Scott D Gitlin, MD 734-615-1623 sgitlin@umich.edu
Contact: Cancer AnswerLine canceranswerline@umich.edu
United States
 
NCT01528865
UMCC 2010 097, HUM 33361
Yes
Scott Gitlin, MD, University of Michigan Cancer Center
University of Michigan Cancer Center
  • GlaxoSmithKline
  • Gilead Sciences
Not Provided
University of Michigan Cancer Center
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP