HIVPhase 1NCT03346499
Adoptive Transfer of Haploidentical Natural Killer Cells and IL-2
A Phase 1 study testing NK cells and IL-2 in people with HIV, run by University of Minnesota at 1 site in United States.
Trial summary
This is a pilot study of the infusion of haploidentical NK cells with IL-2 in 5 HIV+ individuals who are on stable ART with full HIV suppression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV
- What is being tested?
- NK cells and IL-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2017to 13 Nov 2018
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ¥ Age-18-65
- Stable ART for at least 12 months.
- Screening plasma HIV RNA levels below level of quantification (<40 to <50 copies RNA/mL depending on the assay) for ≥ 6 months (a total of 3 measurements above the level of detection but < 500 copies/ml will be allowed if each detectable measure is separated by at least 1 year)
- Screening CD4 count ≥500 cells/µl
- Laboratory tests (CBCD, CMP, Mg, Phosphorus, PT/PTT, TSH/T4,) performed within 14 days of study enrollment. All laboratory results (unless otherwise specified) must be Grade 1 or normal based on the DAIDS Adverse Event Grading Scale (Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.0)
- Adequate kidney function defined by estimated GFR (CrCl) > 60 ml/min or ml/min/1.73 m2 (≤ grade 2 per DAIDS) and creatinine ≤ 1.5 x ULN
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- Adequate pulmonary function without any clinical signs or symptoms of severe pulmonary dysfunction. PFT testing must show FEV1 and DLCOcorr > 50% of predicted if subjects have symptomatic or prior known impairment.
- Transthoracic echocardiogram with PA pressures in the range of 18-26 mmHg
- Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before infusion of cells
- Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
- Voluntary written consent provided by the subject
Who cannot join
- Any condition that precludes lymph node biopsy or colonoscopy with biopsy
- Active infection other than HIV currently requiring systemic antimicrobial therapy
- History of deep vein thrombosis
- Active significant, tissue invasive fungal infection requiring systemic antifungal therapy (dermatologic conditions requiring only topical therapy are allowed).
- Chronic active hepatitis B or C (defined as antibody positive and DNA+ or HepBsAG+).
- Breastfeeding
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- Intended modification of antiretroviral therapy in the next 24 weeks
- NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction
- Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial infarction within 6 months prior to screening
- Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
- On-going chronic systemic corticosteroid use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible and inhaled corticosteroids is allowed. Topical steroids are allowed.)
- Psychiatric illness/social situations that would limit compliance with study requirements
- Previous diagnosis of an autoimmune disease (e.g. rheumatoid arthritis, lupus, inflammatory bowel disease, multiple sclerosis, vasculitis)
- Use of any anticoagulants within the previous 4 weeks.
- Other illness that in the opinion of the investigator would exclude the patient from participating in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
About this study
Official title: Adoptive Transfer of Haploidentical Natural Killer Cells and IL-2 in Human Immunodeficiency Virus (HIV)
This is a pilot study of the infusion of haploidentical NK cells with IL-2 in 5 HIV+ individuals who are on stable ART with full HIV suppression.
Read the detailed description
Potential subjects will be screened to determine eligibility. Immediately after consent and screening, an HLA-haploidentical donor will be identified and will complete eligibility screen and consent. At Day -7 the subject will undergo an inguinal lymph node biopsy and colonoscopy to obtain ileal and rectal biopsies. Blood samples will be obtained to measure chimerisms, plasma HIV RNA, and inflammatory cytokines. PBMCs will be obtained to sort into CD4 subsets and measure frequencies of HIV RNA and DNA. On Day -1, the donor will undergo apheresis and donor cells will be obtained and incubated overnight with IL-2. On Day 0 subjects will start aspirin and be infused with IL-2 activated NK cells. Subjects will receive 6 million units of IL-2 just after the infusion and they will be monitored on the Phase 1 Unit for 24 hours. Plasma will be obtained at 2 hrs, 4 hrs and the following morning and stored for measures of inflammatory markers. The subject will return to the outpatient clinic on days 2, 4, 6, 8, and 10 after the infusion for administration of 6 million units of IL-2 and to obtain plasma and PBMC for measures of inflammatory markers and changes to the virus reservoir. On day 14 the subject will stop taking ASA and blood will be obtained to measure frequencies of HIV RNA and DNA. On day 21 will have a lymph node biopsy and colonoscopy to obtain ileal and rectal tissues. The patient will then be followed until day 100 post NK cell infusion. Subjects will return every 2 weeks for a toxicity assessment, blood draws, and viral level testing. Study participation will end after day 100.
- Conditions
- HIV
- Being tested
- NK cells and IL-2
- Keywords
- HIV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK cells and IL-2Biological
Natural Killer Cells
| Study group | Role | What they receive |
|---|---|---|
| NK cells and IL-2 | Experimental | Not described Receives: Biological: NK cells and IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of administration of haploidentical NK cells in HIV infected individuals - Adverse Events
Subjects will receive haploidentical NK and all adverse events will be collected
Measured: Baseline, 100 days
Tolerability of administration of haploidentical NK cells in HIV infected individuals- Side effects
Side effects from all subjects will be collected
Measured: Baseline, 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start9 Mar 2017
- Primary completion13 Nov 2018
- Study completion13 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy Schacker, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346499
- Sponsor's protocol ID
- 1508M77601-2
- Status last verified
- Nov 2019
- First submitted
- 24 Oct 2017
- Last updated
- 20 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Miller JS, Rhein J, Davis ZB, Cooley S, McKenna D, Anderson J, Escandon K, Wieking G, Reichel J, Thorkelson A, Jorstad S, Safrit JT, Soon-Shiong P, Beilman GJ, Chipman JG, Schacker TW. Safety and Virologic Impact of Haploidentical NK Cells Plus Interleukin 2 or N-803 in HIV Infection. J Infect Dis. 2024 May 15;229(5):1256-1265. doi: 10.1093/infdis/jiad578.
PubMed 38207119
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of Haploidentical Natural Killer Cells and IL-2 in Human Immunodeficiency Virus (HIV)
- ClinicalTrials.gov ID
- NCT03346499
- Acronym / sponsor ID
- 1508M77601-2
- Conditions
- HIV
- Keywords
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 9 Mar 2017 (actual)
- Primary completion
- 13 Nov 2018 (actual)
- Study completion
- 13 Nov 2018 (actual)
- First posted
- 17 Nov 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.
This is a pilot study of the infusion of haploidentical NK cells with IL-2 in 5 HIV+ individuals who are on stable ART with full HIV suppression.
Detailed description
Potential subjects will be screened to determine eligibility. Immediately after consent and screening, an HLA-haploidentical donor will be identified and will complete eligibility screen and consent. At Day -7 the subject will undergo an inguinal lymph node biopsy and colonoscopy to obtain ileal and rectal biopsies. Blood samples will be obtained to measure chimerisms, plasma HIV RNA, and inflammatory cytokines. PBMCs will be obtained to sort into CD4 subsets and measure frequencies of HIV RNA and DNA. On Day -1, the donor will undergo apheresis and donor cells will be obtained and incubated overnight with IL-2. On Day 0 subjects will start aspirin and be infused with IL-2 activated NK cells. Subjects will receive 6 million units of IL-2 just after the infusion and they will be monitored on the Phase 1 Unit for 24 hours. Plasma will be obtained at 2 hrs, 4 hrs and the following morning and stored for measures of inflammatory markers. The subject will return to the outpatient clinic on days 2, 4, 6, 8, and 10 after the infusion for administration of 6 million units of IL-2 and to obtain plasma and PBMC for measures of inflammatory markers and changes to the virus reservoir. On day 14 the subject will stop taking ASA and blood will be obtained to measure frequencies of HIV RNA and DNA. On day 21 will have a lymph node biopsy and colonoscopy to obtain ileal and rectal tissues. The patient will then be followed until day 100 post NK cell infusion. Subjects will return every 2 weeks for a toxicity assessment, blood draws, and viral level testing. Study participation will end after day 100.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK cells and IL-2 | Experimental | Biological: NK cells and IL-2 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- ¥ Age-18-65
Key exclusion criteria (15 listed)
- Any condition that precludes lymph node biopsy or colonoscopy with biopsy
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 |
|---|---|---|
| NK cells and IL-2Natural Killer Cells | Biological | NK cells and IL-2 |
Primary outcome
Safety of administration of haploidentical NK cells in HIV infected individuals - Adverse Events
Time frame: Baseline, 100 days
Subjects will receive haploidentical NK and all adverse events will be collected
Tolerability of administration of haploidentical NK cells in HIV infected individuals- Side effects
Time frame: Baseline, 100 days
Side effects from all subjects will be collected
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Derived from this study: PubMed 38207119Miller JS, Rhein J, Davis ZB, Cooley S, McKenna D, Anderson J, Escandon K, Wieking G, Reichel J, Thorkelson A, Jorstad S, Safrit JT, Soon-Shiong P, Beilman GJ, Chipman JG, Schacker TW. Safety and Virologic Impact of Haploidentical NK Cells Plus Interleukin 2 or N-803 in HIV Infection. J Infect Dis. 2024 May 15;229(5):1256-1265. doi: 10.1093/infdis/jiad578.
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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.
Timothy Schacker, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK cells and IL-2 in people with HIV, run by University of Minnesota at 1 site in United States.
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 11 inclusion and 15 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: finished, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of administration of haploidentical NK cells in HIV infected individuals - Adverse Events (time frame: Baseline, 100 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03346499, which also lists 1 linked publication.
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 20 Nov 2019.