Clinical trial NCT03118661: Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: HIV-1-infection
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2017-04-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility 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.

Primary outcomes:
measure: HIV-1 proviral DNA levels in peripheral blood
timeFrame: Up to week 16 after transplant
measure: HIV-1 reactivation in stimulated assay
timeFrame: Up to week 16 after transplant
measure: Presence and severity of GvHD
timeFrame: Through 5 years after transplant
measure: Time to hematopoietic cell and immune recovery
timeFrame: Up to 100 days after transplant
measure: Number of participants who experience chimerism
timeFrame: At the time of screening
measure: Survival of participants
timeFrame: 100 days after transplant
measure: Survival of participants
timeFrame: Week 26 after transplant
measure: Survival of participants
timeFrame: Week 52 after transplant
measure: Survival of participants
timeFrame: 5 years after transplant
measure: Event free survival
timeFrame: 100 days after transplant
measure: Event free survival
timeFrame: Week 26 after transplant
measure: Event free survival
timeFrame: Week 52 after transplant
measure: Event free survival
timeFrame: 5 years after transplant
Secondary outcomes:
measure: Number of participants who achieve a state of functional cure
timeFrame: Through 5 years after transplant
measure: Number of participants who achieve a state of sterilizing cure
timeFrame: Through 5 years after transplant
measure: Number of participants who have plasma viral load <50 copies/ml
timeFrame: Through 5 years after transplant
measure: Number of participants who have existence of replication competent HIV-1 reservoirs in peripheral blood, gut and other tissue compartments
timeFrame: Through 5 years after transplant
measure: Number of participants who have gut immune reconstitution
timeFrame: Through 5 years after transplant
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: Rachel M Presti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: