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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01620736
First received: January 25, 2012
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Human T-cell Leukemia Virus Type 1 Infection
Drug: Raltegravir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Effects of raltegravir on HTLV-1 provirus load in asymptomatic individuals [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
    1. 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
    2. 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 [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 wks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 wks ] [ Designated as safety issue: Yes ]
    Assessed by physical exam, CBC, and serum chemistries on days 29 and 57 and


Estimated Enrollment: 14
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir
Treatment with raltegravir for 8 wks
Drug: Raltegravir
Raltegravir 400 mg po bid

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01620736

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94118
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Lee Ratner, MD PhD Washington University School of Medicine
  More Information

Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01620736     History of Changes
Other Study ID Numbers: WashU201109171
Study First Received: January 25, 2012
Last Updated: June 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Raltegravir
HTLV
Integrase

Additional relevant MeSH terms:
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 01, 2014