HIV-1-infectionPhase 1NCT03118661
Maraviroc on HIV-1 Infected Subjects Who Require Allogeneic Hematopoietic Cell Transplant
A Phase 1 study testing For Step 2: Structured treatment interruption and Peripheral blood draw in people with HIV-1-infection, run by Washington University School of Medicine.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- For Step 2: Structured treatment interruption and Peripheral blood draw
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 19 Mar 2018to 30 Sep 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- Ongoing AIDS-related opportunistic infection (including oral thrush).
- Pregnant and/or breastfeeding.
About this study
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
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
- Being tested
- For Step 2: Structured treatment interruption, Peripheral blood draw
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
For Step 2: Structured treatment interruptionOther
Also called STI
-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection
Peripheral blood drawProcedure or surgery
-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
| Study group | Role | What they receive |
|---|---|---|
| Maraviroc after allo-HCT | Experimental | * 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 Receives: Other: For Step 2: Structured treatment interruption; Procedure: Peripheral blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-1 proviral DNA levels in peripheral blood
- Obtained from peripheral blood
- Used to determine if participant can proceed to Step 2
Measured: Up to week 16 after transplant
HIV-1 reactivation in stimulated assay
- Obtained from peripheral blood
- Used to determine if participant can proceed to Step 2
Measured: Up to week 16 after transplant
Presence and severity of GvHD
-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
Measured: Through 5 years after transplant
Time to hematopoietic cell and immune recovery
-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.
Measured: Up to 100 days after transplant
Number of participants who experience chimerism
-Chimerism is measured by ≥ 98% of blood cells donor derived
Measured: At the time of screening
Survival of participants
-Number of participants who are alive 100 days after transplant
Measured: 100 days after transplant
Survival of participants
-Number of participants who are alive 26 weeks after transplant
Measured: Week 26 after transplant
Survival of participants
-Number of participants who are alive 52 weeks after transplant
Measured: Week 52 after transplant
Survival of participants
-Number of participants who are alive 5 years after transplant
Measured: 5 years after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Measured: 100 days after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Measured: Week 26 after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Measured: Week 52 after transplant
Event free survival
-Defined as survival where the cancer does not recur, the graft takes, and there are no life-threatening events
Measured: 5 years after transplant
Secondary outcomes (5)
Number of participants who achieve a state of functional cure
-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.
Measured: Through 5 years after transplant
Number of participants who achieve a state of sterilizing cure
-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
Measured: Through 5 years after transplant
Number of participants who have plasma viral load <50 copies/ml
-Obtained from peripheral blood
Measured: 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
-Obtained from peripheral blood
Measured: Through 5 years after transplant
Number of participants who have gut immune reconstitution
-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
Measured: Through 5 years after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start19 Mar 2018
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Why it stopped: No accrual to the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachel M Presti, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03118661
- Sponsor's protocol ID
- 201704019
- Status last verified
- Nov 2018
- First submitted
- 13 Apr 2017
- Last updated
- 7 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03118661
- Acronym / sponsor ID
- 201704019
- Conditions
- HIV-1-infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No accrual to the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 19 Mar 2018 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 18 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Maraviroc after allo-HCT | Experimental | Other: For Step 2: Structured treatment interruption, Procedure: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (2 listed)
- Ongoing AIDS-related opportunistic infection (including oral thrush).
- Pregnant and/or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| For Step 2: Structured treatment interruptionAlso: STI-Accepted tool in the evaluation of immunological interventions, gene therapy, or therapeutic vaccines for the treatment of HIV infection | Other | Maraviroc after allo-HCT |
| 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 | Procedure or surgery | Maraviroc after allo-HCT |
Primary outcome
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
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
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
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.
Number of participants who experience chimerism
Time frame: At the time of screening
-Chimerism is measured by ≥ 98% of blood cells donor derived
Survival of participants
Time frame: 100 days after transplant
-Number of participants who are alive 100 days after transplant
Survival of participants
Time frame: Week 26 after transplant
-Number of participants who are alive 26 weeks after transplant
Survival of participants
Time frame: Week 52 after transplant
-Number of participants who are alive 52 weeks after transplant
Survival of participants
Time frame: 5 years after transplant
-Number of participants who are alive 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
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
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
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 secondary outcomes
Number of participants who achieve a state of functional cure
Time frame: Through 5 years after transplant
Number of participants who achieve a state of sterilizing cure
Time frame: Through 5 years after transplant
Number of participants who have plasma viral load <50 copies/ml
Time frame: 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
Number of participants who have gut immune reconstitution
Time frame: Through 5 years after transplant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2018.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel M Presti, M.D. principal investigator
Washington University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing For Step 2: Structured treatment interruption and Peripheral blood draw in people with HIV-1-infection, run by Washington University School of Medicine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HIV-1 proviral DNA levels in peripheral blood (time frame: Up to week 16 after transplant). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2018.