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

Phase 1

Withdrawn

• Conditions: HIV-1-infection
• Interventions: Procedure: Peripheral blood draw

• Registration Number: NCT03118661
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-13
• Study First Submitted QC: 2017-04-13
• Study First Posted: 2017-04-18
• Study Start: 2018-03-19
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-06
• Last Update Posted: 2018-11-07
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

• Ongoing AIDS-related opportunistic infection (including oral thrush).
• Pregnant and/or breastfeeding.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Maraviroc after allo-HCT	Peripheral blood draw	* 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

Primary Outcome Measures

Name	Time	Method
Time to hematopoietic cell and immune recovery	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.
Number of participants who experience chimerism	At the time of screening	-Chimerism is measured by ≥ 98% of blood cells donor derived
Survival of participants	5 years after transplant	-Number of participants who are alive 5 years after transplant
Event free survival	5 years after transplant	-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
HIV-1 proviral DNA levels in peripheral blood	Up to week 16 after transplant	* Obtained from peripheral blood; * Used to determine if participant can proceed to Step 2
Presence and severity of GvHD	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
HIV-1 reactivation in stimulated assay	Up to week 16 after transplant	* Obtained from peripheral blood; * Used to determine if participant can proceed to Step 2

Secondary Outcome Measures

Name	Time	Method
Number of participants who achieve a state of functional cure	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.
Number of participants who achieve a state of sterilizing cure	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
Number of participants who have plasma viral load <50 copies/ml	Through 5 years after transplant	-Obtained from peripheral blood
Number of participants who have gut immune reconstitution	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
Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments	Through 5 years after transplant	-Obtained from peripheral blood