Safety & Efficacy of Lamivudine & Tenofovir to Lower Plasma Level of Viral RNA in Lymphoma
| Status: | Withdrawn |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | December 2015 |
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 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.
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.
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 reverse transcriptase
polymerase chain reaction (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 Eastern Cooperative Oncology Group (ECOG) 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 disoproxil fumarate
(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
We found this trial at
1
site
1500 East Medical Center Drive
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
800-865-1125
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
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