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

NCT ID: NCT03118661

Last Updated: 2018-11-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-19
• Study Completion Date: 2025-09-30

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.

Conditions

HIV-1-infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

For Step 2: Structured treatment interruption

Intervention Type: OTHER

-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection

Peripheral blood draw

Intervention Type: PROCEDURE

-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

Interventions

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

Intervention Type: OTHER

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

Intervention Type: PROCEDURE

Other Intervention Names

STI

Eligibility Criteria

Inclusion Criteria

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel M Presti, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201704019

Identifier Type: -

Identifier Source: org_study_id