Clinical trial NCT01620736: Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load
Official title: Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Human T-cell Leukemia Virus Type 1 Infection
Keywords: Raltegravir
HTLV
Integrase
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-06-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study of the effect of raltegravir on human T-cell leukemia virus type 1 (HTLV-1) viral load in asymptomatic patients. The study will enroll 14 subjects for a period of 2 months of treatment and 1 month of followup. The study will assess the effect of raltegravir on virus load in peripheral blood lymphocytes, level of virus gene expression, and sites of viral integration.

Detailed description: About 5% of HTLV-1 infected individuals develop lymphoma or myelopathy. High levels of virus replication are predictive of disease development. HTLV-1 exhibits lower levels of variation than HIV-1, suggesting that drug resistance is less likely to occur. Raltegravir was shown to inhibit HTLV-1 integration and replication in culture using concentrations achievable with the approved dose used in HIV-1 infected patients. Currently, no treatment is recommended for asymptomatic infected individuals.

Eligibility criteria: Inclusion Criteria:

1. Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Western blot) and confirmed to be HTLV-1 rather than HTLV-2 by differential Western blot (e.g. Genelabs Diagnostics HTLV Blot 2.4) or PCR.
2. Adequate hematologic function within 14 days before enrollment: ANC \> 1000 cells/mm3, platelet count \> 75,000 cells/mm3.
3. Adequate hepatic function, transaminase \< 3 times the upper limit of normal; bilirubin \< 2.0.
4. Creatinine \< 2.0
5. Karnofsky Performance Status at least 70
6. Age at least 18.
7. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
8. Female patients of child bearing potential must have a negative pregnancy test within 72 hrs of initiation of therapy. Female patients are either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study. Male patients must agree to use two acceptable methods for contraception for the duration of the study. Women must avoid pregnancy and men avoid fathering children while in the study.
9. Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

1. Acute active infection requiring therapy. Chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met.
2. Women who are pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
3. Patient has received other investigational drugs with 14 days before enrollment
4. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Primary outcomes:
measure: Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals
timeFrame: 8 wks
Secondary outcomes:
measure: Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations
timeFrame: 8 wks
measure: Effects of raltegravir on number of LTR circles and level of proviral RNA expression in PBMCs
timeFrame: 8 wks
measure: Effects of raltegravir on viral integrase gene or other viral sequence changes
timeFrame: 8 wks
measure: Effect of raltegravir on viral integration sites
timeFrame: 8 wks
measure: Tolerance of raltegravir in HTLV-1 infected individuals
timeFrame: 8 wks
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: Lee Ratner, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seegulam ME, Ratner L. Integrase inhibitors effective against human T-cell leukemia virus type 1. Antimicrob Agents Chemother. 2011 May;55(5):2011-7. doi: 10.1128/AAC.01413-10. Epub 2011 Feb 22.