- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03118661
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
Withdrawn
Conditions
Intervention / Treatment
Study Type
Interventional
Phase
- 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
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 |
Intervention / Treatment |
---|---|
Experimental: Maraviroc after allo-HCT
|
-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection
Other Names:
-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
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HIV-1 proviral DNA levels in peripheral blood
Time Frame: Up to week 16 after transplant
|
|
Up to week 16 after transplant
|
HIV-1 reactivation in stimulated assay
Time Frame: Up to week 16 after transplant
|
|
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
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.
Investigators
- 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.
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)
March 19, 2018
Primary Completion (Anticipated)
September 30, 2025
Study Completion (Anticipated)
September 30, 2025
Study Registration Dates
First Submitted
April 13, 2017
First Submitted That Met QC Criteria
April 13, 2017
First Posted (Actual)
April 18, 2017
Study Record Updates
Last Update Posted (Actual)
November 7, 2018
Last Update Submitted That Met QC Criteria
November 6, 2018
Last Verified
November 1, 2018
More Information
Terms related to this study
Other Study ID 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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