Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03118661
Recruitment Status : Withdrawn (No accrual to the study)
First Posted : April 18, 2017
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The goal of this proposal is to determine the effect of maraviroc when it has been a part of the antiretroviral (ART) regimen given immediately after allogeneic hematopoietic cell transplant (allo-HCT) for HIV-1 infected participants who have a hematopoietic malignancy or other underlying disorder requiring an allogeneic transplant. Maraviroc has been given in practice to alleviate symptoms of graft vs. host disease (GvHD). Given its mechanism of action, it may also have an effect on the reservoir size of HIV-1 in infected patients. This study will inform potential future studies, evaluating the effect of this approach on the incidence and severity of GvHD, and determining its effect on HIV-1 reservoir.

Condition or disease Intervention/treatment Phase
HIV-1-infection Other: For Step 2: Structured treatment interruption Procedure: Peripheral blood draw Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Effect of CCR5 Inhibition by Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant for Any Indication and Its Observed Effect on Graft Versus Host Disease and HIV-1 Persistence
Actual Study Start Date : March 19, 2018
Estimated Primary Completion Date : September 30, 2025
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Maraviroc

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Maraviroc after allo-HCT
  • Step 1: participants who have received at least 30 days of maraviroc immediately post allo-HCT can be enrolled. Blood will be drawn at 2 time points at least 2 weeks apart, but within 4 weeks, and assessed for HIV-1 reservoir using both DNA assays and cell-associated reactivation by infectivity after stimulation. If any biopsies post allo-HCT are performed as part of standard of care and available, these will also be assessed for HIV-1
  • Step 2: If HIV-1 reservoir is undetecable, antiretrovirals (ART) will be stopped in a structured treatment interruption (STI). HIV-1 VLs and CD4+ T-cells check weekly. Week 16, participants will have a large volume blood draw if remain suppressed. If confirmed return of viremia, ART will be reinitiated and he/she will be followed until HIV VL is <50 copies/ml. If he/she remains suppressed at Week 16 and repeat assays confirm no detectable HIV-1, HIV-1 VLs and CD4+ T-cell counts will be checked monthly until Week 52, and then quarterly until Year 5
 Other: For Step 2: Structured treatment interruption
-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection
Other Name: STI

Procedure: Peripheral blood draw
-Screening, entry for Step 1, Step 1 visit 2, entry for Step 2, weekly, week 16, monthly through week 52, week 52, quarterly through year 5, year 5, and viral relapse


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. HIV-1 proviral DNA levels in peripheral blood [ Time Frame: Up to week 16 after transplant ]
    • Obtained from peripheral blood
    • Used to determine if participant can proceed to Step 2

  2. HIV-1 reactivation in stimulated assay [ Time Frame: Up to week 16 after transplant ]
    • Obtained from peripheral blood
    • Used to determine if participant can proceed to Step 2

  3. Presence and severity of GvHD [ Time Frame: Through 5 years after transplant ]
    -GvHD will be measured using the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: IV. Response Criteria Working Group Report

  4. Time to hematopoietic cell and immune recovery [ Time Frame: Up to 100 days after transplant ]
    -In general, the mean time of engraftment of the donor cells is approximately 90 to 100 days post-transplant and this can be monitored by measuring the percent chimerism of donor cells.

  5. Number of participants who experience chimerism [ Time Frame: At the time of screening ]
    -Chimerism is measured by ≥ 98% of blood cells donor derived

  6. Survival of participants [ Time Frame: 100 days after transplant ]
    -Number of participants who are alive 100 days after transplant

  7. Survival of participants [ Time Frame: Week 26 after transplant ]
    -Number of participants who are alive 26 weeks after transplant

  8. Survival of participants [ Time Frame: Week 52 after transplant ]
    -Number of participants who are alive 52 weeks after transplant

  9. Survival of participants [ Time Frame: 5 years after transplant ]
    -Number of participants who are alive 5 years after transplant

  10. Event free survival [ Time Frame: 100 days after transplant ]
    -Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events

  11. Event free survival [ Time Frame: Week 26 after transplant ]
    -Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events

  12. Event free survival [ Time Frame: Week 52 after transplant ]
    -Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events

  13. Event free survival [ Time Frame: 5 years after transplant ]
    -Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events


Secondary Outcome Measures :
  1. Number of participants who achieve a state of functional cure [ Time Frame: Through 5 years after transplant ]
    -Functional Cure: Following the discontinuation of all HIV-1 related treatment interventions, including HAART, a participant will be considered to have achieved an HIV-1 functional cure if for at least 5 years they: maintain an undetectable plasma viral load, using standard clinical assays, have achieved full CD4+ lymphocyte recovery with normal levels of T cell activation and proliferation, and normal levels of immunoglobulins with no disease progression. It is anticipated that participants who have achieved a functional cure will continue to have detectable HIV-1 DNA in peripheral blood cells and/or tissues.

  2. Number of participants who achieve a state of sterilizing cure [ Time Frame: Through 5 years after transplant ]
    -Sterilizing cure: same definition of functional cure but no detectable replication-competent virus in peripheral blood and minimal (near limits of detection) HIV-1 DNA in peripheral blood and or tissue

  3. Number of participants who have plasma viral load <50 copies/ml [ Time Frame: Through 5 years after transplant ]
    -Obtained from peripheral blood

  4. Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments [ Time Frame: Through 5 years after transplant ]
    -Obtained from peripheral blood

  5. Number of participants who have gut immune reconstitution [ Time Frame: Through 5 years after transplant ]
    -Will consist of tissue immunohistochemistry to analyze CD4 T cells when feasible, and for plasma markers of gut microbial translocation namely lipopolysaccharide (LPS) and soluble CD14 (sCD14) a marker of monocyte activation attributed to LPS effects


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Step 1)

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
  • Receipt of allo-HCT for any indication at least 100 days prior to study entry.
  • Receipt of maraviroc for at least 30 days starting at date of transplant. Longer receipt of maraviroc is acceptable. Documentation of HIV-1 tropism for CCR5 should be obtained if available, but it is not necessary that the participant have prior CCR5-tropic.
  • At least 18 years of age.
  • HIV-1 RNA that is <50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.
  • For females of reproductive potential (i.e., women who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative urine pregnancy test (with a sensitivity of 15-25 mIU/mL) within 48 hours prior to screening and entry.
  • Negative HBsAg result obtained within 6 months prior to study entry, or documentation of HBV immunity by positive HBV sAb at any time

  • The following laboratory values obtained within 45 days prior to enrollment:

    • CD4+ T cell count >250 cells/ mm^3
    • Absolute neutrophil count (ANC) ≥1000 cells/mm^3
    • Hemoglobin ≥10.0 g/dL for men and ≥9.0 g/dL for women
    • Platelet count ≥ 50,000/mm3
  • Ability and willingness of participant or legal representative to provide informed consent.

Additional Inclusion Criteria for Step 2 of Study:

  • HIV-1 latent reservoir undetectable by co-culture and DNA
  • No confirmed detectable HIV-1 RNA > 1000 cells/mm3 since discontinuation of maraviroc
  • Prior HIV-1 genotype results that confirm that there are active agents available in at least three classes of ART drugs (NRTI, NNRTI, PI or integrase).
  • Willing to stop ART
  • Willing to undergo high volume blood draw (125 cc) at Week 16
  • Willing to restart ART if HIV-1 viremia returns
  • Provide informed consent for Step 2

Exclusion Criteria:

  • Ongoing AIDS-related opportunistic infection (including oral thrush).
  • Pregnant and/or breastfeeding.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03118661


Sponsors and Collaborators
Washington University School of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Rachel M Presti, M.D. Washington University School of Medicine
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03118661    
Other Study ID Numbers: 201704019
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No