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Withdrawn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
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
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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
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
NCT ID
NCT01620736
First Posted
January 25, 2012
Last Updated
January 22, 2018
Sponsor
Washington University School of Medicine
Collaborators
Merck Sharp & Dohme LLC
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.
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Trial to Assess Effect of Raltegravir on HTLV-1 Proviral Load
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