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
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: Lamivudine
Drug: Tenofovir disoproxil fumarate
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Study Start Date: May 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01528865

Contacts
Contact: Scott D Gitlin, MD 734-615-1623 sgitlin@umich.edu
Contact: Cancer AnswerLine canceranswerline@umich.edu

Locations
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         
Sponsors and Collaborators
University of Michigan Cancer Center
GlaxoSmithKline
Gilead Sciences
  More Information

No publications provided

Responsible Party: Scott Gitlin, MD, Principal Investigator, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01528865     History of Changes
Other Study ID Numbers: UMCC 2010 097, HUM 33361
Study First Received: January 12, 2012
Last Updated: March 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
virus
K(HML2)[HERV-K(HML2)]
Lymphoma
Human endogenous retrovirus-K(HLM2)[HERV-K(HML2)]

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lamivudine
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014