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

November 6, 2018 updated by: Washington University School of Medicine

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to week 16 after transplant
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
Up to week 16 after transplant
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
Through 5 years after transplant
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.
Up to 100 days after transplant
Number of participants who experience chimerism
Time Frame: At the time of screening
-Chimerism is measured by ≥ 98% of blood cells donor derived
At the time of screening
Survival of participants
Time Frame: 100 days after transplant
-Number of participants who are alive 100 days after transplant
100 days after transplant
Survival of participants
Time Frame: Week 26 after transplant
-Number of participants who are alive 26 weeks after transplant
Week 26 after transplant
Survival of participants
Time Frame: Week 52 after transplant
-Number of participants who are alive 52 weeks after transplant
Week 52 after transplant
Survival of participants
Time Frame: 5 years after transplant
-Number of participants who are alive 5 years after transplant
5 years after transplant
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
100 days after transplant
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
Week 26 after transplant
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
Week 52 after transplant
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
5 years after transplant

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Through 5 years after transplant
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
Through 5 years after transplant
Number of participants who have plasma viral load <50 copies/ml
Time Frame: Through 5 years after transplant
-Obtained from peripheral blood
Through 5 years after transplant
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
Through 5 years after transplant
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
Through 5 years after transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rachel M Presti, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 19, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201704019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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