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Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Primary Purpose

Human T-cell Leukemia Virus Type 1 Infection

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Raltegravir
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human T-cell Leukemia Virus Type 1 Infection focused on measuring Raltegravir, HTLV, Integrase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Raltegravir

    Arm Description

    Treatment with raltegravir for 8 wks

    Outcomes

    Primary Outcome Measures

    Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals
    Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.

    Secondary Outcome Measures

    Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations
    Measured by real time PCR with DNA from sorted peripheral blood mononuclear cell DNA at days 1, 8, 15, 29, 43, and 56.
    Effects of raltegravir on number of LTR circles and level of proviral RNA expression in PBMCs
    Number of LTR circles measure by real time PCR on peripheral blood mononculear cell DNA at days 0, 1, 8, 15, 29, 43, and 56 Level of Proviral RNA Expression in PBMCs measured by real time RT PCR on peripheral blood mononculear cell RNA at days 0, 1, 8, 15, 29, 43, and 56
    Effects of raltegravir on viral integrase gene or other viral sequence changes
    Measured by automated sequence analysis of PCR amplified viral DNA obtained at days 0, 1, 8, 15, 29, 43, and 56
    Effect of raltegravir on viral integration sites
    Measured by automated DNA analysis of oligonucleotide linked PCR amplified DNA from peripheral blood mononuclear cell DNA obtianed at days 0, 1, 8, 15, 29, 43,and 56
    Tolerance of raltegravir in HTLV-1 infected individuals
    Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and

    Full Information

    First Posted
    January 25, 2012
    Last Updated
    January 22, 2018
    Sponsor
    Washington University School of Medicine
    Collaborators
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01620736
    Brief Title
    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

    2. Study Status

    Record Verification Date
    January 2018
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    The clinical trial did not receive any funding.
    Study Start Date
    January 2012 (undefined)
    Primary Completion Date
    December 2013 (Anticipated)
    Study Completion Date
    December 2014 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Washington University School of Medicine
    Collaborators
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Human T-cell Leukemia Virus Type 1 Infection
    Keywords
    Raltegravir, HTLV, Integrase

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Raltegravir
    Arm Type
    Experimental
    Arm Description
    Treatment with raltegravir for 8 wks
    Intervention Type
    Drug
    Intervention Name(s)
    Raltegravir
    Intervention Description
    Raltegravir 400 mg po bid
    Primary Outcome Measure Information:
    Title
    Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals
    Description
    Measured by DNA PCR from peripheral blood mononuclear cell DNA at days 0, 1, 8, 15, 29, 43, and 56.
    Time Frame
    8 wks
    Secondary Outcome Measure Information:
    Title
    Effects of raltegravir on proviral load in CD4+CD25+, CD4+CD25-, and CD8+ cell populations
    Description
    Measured by real time PCR with DNA from sorted peripheral blood mononuclear cell DNA at days 1, 8, 15, 29, 43, and 56.
    Time Frame
    8 wks
    Title
    Effects of raltegravir on number of LTR circles and level of proviral RNA expression in PBMCs
    Description
    Number of LTR circles measure by real time PCR on peripheral blood mononculear cell DNA at days 0, 1, 8, 15, 29, 43, and 56 Level of Proviral RNA Expression in PBMCs measured by real time RT PCR on peripheral blood mononculear cell RNA at days 0, 1, 8, 15, 29, 43, and 56
    Time Frame
    8 wks
    Title
    Effects of raltegravir on viral integrase gene or other viral sequence changes
    Description
    Measured by automated sequence analysis of PCR amplified viral DNA obtained at days 0, 1, 8, 15, 29, 43, and 56
    Time Frame
    8 wks
    Title
    Effect of raltegravir on viral integration sites
    Description
    Measured by automated DNA analysis of oligonucleotide linked PCR amplified DNA from peripheral blood mononuclear cell DNA obtianed at days 0, 1, 8, 15, 29, 43,and 56
    Time Frame
    8 wks
    Title
    Tolerance of raltegravir in HTLV-1 infected individuals
    Description
    Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and
    Time Frame
    8 wks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Adequate hematologic function within 14 days before enrollment: ANC > 1000 cells/mm3, platelet count > 75,000 cells/mm3. Adequate hepatic function, transaminase < 3 times the upper limit of normal; bilirubin < 2.0. Creatinine < 2.0 Karnofsky Performance Status at least 70 Age at least 18. 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. 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. Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial. Exclusion Criteria: Acute active infection requiring therapy. Chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met. 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. Patient has received other investigational drugs with 14 days before enrollment Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lee Ratner, MD PhD
    Organizational Affiliation
    Washington University School of Medicine
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    21343468
    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.
    Results Reference
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    Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

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