HivPhase 1NCT03899480
Adoptive Transfer of Haploidentical NK Cells and N-803
A Phase 1 study testing Haploidentical Natural Killer (NK) Cells in people with Hiv and HIV Infections, run by University of Minnesota at 1 site in United States.
Trial summary
This is a pilot therapeutic study of related donor HLA-haploidentical NK-cell based therapy to determine if the treatment is safe and well-tolerated and if there is any measureable impact on virus reservoirs. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hiv, HIV Infections, Immune Deficiency
- What is being tested?
- Haploidentical Natural Killer (NK) Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 1 Apr 2021
- 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).
- Screening CD4 count ≥500 cells/µl
- Laboratory tests (Complete Blood Count, Comprehensive Metabolic Panel, Mg, Phosphorus, international normalized ratio/partial thromboplastin time (INR/PTT), Thyroid stimulating hormone (TSH)/T4,) performed within 14 days of infusion of donor NK cells. 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 Glomerular Filtration Rate (CrCl) > 60 ml/min or ml/min/1.73 m2 (≤ grade 2 per DAIDS) and creatinine ≤ 1.5 x ULN
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- Pulmonary Function Testing (PFT) must show FEV1 and DLCOcorr > 50% of predicted if subjects have symptomatic or prior known impairment.
- Normal transthoracic echocardiogram
- 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 leukapheresis, 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
Show all 15Show fewer
- 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
Minneapolis, Minnesota, 55455
About this study
Official title: Adoptive Transfer of Haploidentical Natural Killer Cells and IL-15 Super Agonist ALT-803 in Human Immunodeficiency Virus (HIV)
This is a pilot therapeutic study of related donor HLA-haploidentical NK-cell based therapy to determine if the treatment is safe and well-tolerated and if there is any measureable impact on virus reservoirs.
Read the detailed description
Human immunodeficiency virus (HIV) infection causes profound and often irreversible changes to the adaptive and innate immune system. In the absence of antiretroviral therapy (ART), Cluster of Differentiation (CD)4+ T cells are progressively depleted, CD8+ T cells are often expanded, and much of the immune system is chronically activated. Much of these abnormalities improve during long-term ART, but the system rarely returns to normal. Notably, chronic inflammation persists indefinitely during ART, and is driven by multiple factors, including HIV production (and perhaps replication), irreversible loss of the mucosal integrity and exposure to gut microbes, and an excess burden of other pathogens such as cytomegalovirus (CMV). How the virus and its host interact during effective ART is the focus of intense investigation.
HIV-1 preferentially infects activated memory CD4+ T cells that express the chemokine receptor CCR5, although resting CD4+ T cells, naïve CD4+ T cells and macrophages can also be infected. The majority of infected and activated CD4+ T cells die quickly, but a small fraction reverts to a resting state and persistent indefinitely as the latent reservoir. Because ART blocks all or nearly all new infection events, the reservoir that exists at the time ART is initiated becomes the reservoir that persists for the life of the individual. This memory T cell viral reservoir is maintained during ART by the long half-life of the infected cell, homeostatic proliferation of these cells and perhaps by low levels of persistent viral replication.
The viral reservoir in peripheral blood exists predominantly in those longer-lived memory CD4+ cells endowed with regenerative potential, including memory stem cells, central memory cells and transitional memory. The reservoir also persists in potentially shorter-lived CD4+ T effector cell populations, but whether these cells represent a stable reservoir or one that is constantly being regenerated via proliferation and differentiation is unknown.
"Shock and Kill". One approach to curing HIV infection that has generated broad support in the field is to induce latently infected cells to produce virus (the "shock") while enhancing the ability of the host to clear these virus-producing cells (the "kill"). Histone deacetylase (HDAC) inhibitors have been shown to increase production of HIV-1 RNA and to a lesser degree virus particles from the viral reservoir in vivo. The magnitude of the effect of HDAC inhibitors is modest at best, and as of yet this class of drugs has had no consistent effect on the frequency of cells that harbor replication-competent HIV. Other classes of anti-latency drugs and immunomodulators are therefore being explored for their capacity to stimulate the viral reservoir.
To augment the capacity of the host to eliminate reservoir cells following activation, several immunologic strategies are being explored. These strategies include therapeutic vaccines, monoclonal antibodies, and immune checkpoint inhibitors.
- Conditions
- Hiv, HIV Infections, Immune Deficiency
- Being tested
- Haploidentical Natural Killer (NK) Cells
- Keywords
- Suppressive Antiretroviral Therapy (ART)
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical Natural Killer (NK) CellsBiological
infusion with N-803 activated NK cells
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical Natural Killer Cells | Experimental | Day -7 the subject will undergo inguinal lymph node biopsy \& colonoscopy to obtain ileal \& rectal biopsies. Blood samples will be obtained. PBMCs will be obtained to sort into CD4 subsets \& measure frequencies of HIV RNA \& DNA. On Day -1, the donor will undergo apheresis \& donor cells will be obtained \& incubated overnight. On Day 0 subjects will be infused with N-803 activated NK cells. Subjects will receive 1st dose of N-803 4 hrs after the infusion. Plasma will be obtained at 2, 4 \& 12 hrs after. Subjects will return on Days 2, 4, 7, 10, \& 14 for blood draw. Subjects will return Days 21 \& 42 for blood work \& to receive 2 additional doses of N-803, for a total of 3 doses. Subjects will be monitored for toxicity assessment by targeted physical exam \& laboratory evaluations on Days 2, 4, 7, 10, 21, \& 42. On day 49, we will perform lymph node biopsy \& colonoscopy to obtain ileal \& rectal tissues. The patient will then be followed until day 100 post infusion. Receives: Biological: Haploidentical Natural Killer (NK) Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Toxicity and adverse events will be classified according to Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.0. Scale ranges from grade 0 to 4 with a grade of 0 indicating normal signs and symptoms and a grade of 4 indicating potentially life-threatening signs and symptoms. Grade 2, 3, and 4 adverse events will be considered when determining the safety and tolerability of treatment.
Measured: throughout trial participation: 100 days post infusion
CBC; White Blood Cell Count
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. White blood cell count will be evaluated by principle investigator. WBC outside of established clinical reference range (4.5-11.0 k/ul) may indicate adverse treatment reaction. Total occurrence of abnormal CBC results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CBC; Red Blood Cell Count
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Red blood cell count will be evaluated by principle investigator. RBC outside established clinical reference range (2.5-5.5 mil/ul) may indicate adverse treatment reaction. Total occurrence of abnormal CBC results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 day post infusion
CBC; Hemoglobin
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Hemoglobin will be evaluated by principle investigator. Hemoglobin outside established clinical reference range (14-17 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal hemoglobin results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CBC; Hematocrit
Complete blood count will be performed at days 2, 3, 10, 21 post infusion. Hematocrit will be evaluated by principle investigator. Hematocrit outside established clinical reference range (42-52%) may indicate adverse treatment reaction. Total occurrence of abnormal hematocrit results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CBC; Mean Corpuscular Volume
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCV will be evaluated by principle investigator. MCV outside established clinical reference range (84-96 fl.) may indicate adverse treatment reaction. Total occurrence of abnormal MCV results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CBC; Mean Corpuscular Hemoglobin
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCH will be evaluated by principle investigator. MCH outside established clinical reference range (28-34 pg) may indicate adverse treatment reaction. Total occurrence of abnormal MCH results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CBC; Mean Corpuscular Hemoglobin Concentration
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCHC will be evaluated by principle investigator. MCHC outside established clinical reference range (33-36 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal MCHC results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Sodium
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Sodium concentration will be evaluated by principle investigator. Sodium concentration outside established clinical reference range (136-145 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal sodium concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Potassium
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Potassium concentration will be evaluated by principle investigator. Potassium concentration outside established clinical reference range (3.5-5.1 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal potassium concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Chloride
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Chloride concentration will be evaluated by principle investigator. Chloride concentration outside established clinical reference range (98-107 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal chloride concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Glucose
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Glucose concentration will be evaluated by principle investigator. Glucose concentration outside established clinical reference range (70-99 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal glucose concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Calcium
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Calcium concentration will be evaluated by principle investigator. Calcium concentration outside established clinical reference range (8.2-10.2 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal calcium concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Blood Urea Nitrogen
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. BUN concentration will be evaluated by principle investigator. BUN concentration outside established clinical reference range (6-25 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal BUN concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Creatinine
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Creatinine concentration will be evaluated by principle investigator. Creatinine concentration outside established clinical reference range (0.8-1.3 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal creatinine concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Alkaline Phosphatase
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Alkaline phosphatase concentration will be evaluated by principle investigator. Alkaline phosphatase concentration outside established clinical reference range (26-137 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal alkaline phosphatase concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Alanine Transaminase
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Alanine transaminase concentration will be evaluated by principle investigator. Alanine transaminase concentration outside established clinical reference range (15-65 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal alanine transaminase concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Aspartate Transaminase
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Aspartate transaminase concentration will be evaluated by principle investigator. Aspartate transaminase concentration outside established clinical reference range (0-37 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal aspartate transaminase concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Total Bilirubin
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Total bilirubin concentration will be evaluated by principle investigator. Total bilirubin concentration outside established clinical reference range (<1.1 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal total bilirubin concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Albumin
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Serum albumin will be evaluated by principle investigator. Serum albumin concentration outside established clinical reference range (3.2-4.7 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal serum albumin concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
CMP; Total Protein
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Total protein will be evaluated by principle investigator. Total protein concentration outside established clinical reference range (6.4-8.2 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal total protein concentration results will be used to determine treatment safety and tolerability.
Measured: 2, 3, 10, and 21 days post infusion
Secondary outcomes (1)
Decrease in HIV reservoirs
The secondary outcomes in this study are quantities of virus in well-defined anatomical locations (gut and lymph node). These quantities will be determined before and after administration of the NK cells and N-803 therapy based on RNAscope and DNAscope, which are technologies that measure concentration of target RNA and DNA.
Measured: 100 days post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start1 May 2019
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
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
- Model description
- Non-controlled intervention groups
- Masking
- None (open label)
- Enrolment
- 9 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
- NCT03899480
- Sponsor's protocol ID
- IDIM-2018-26587
- Status last verified
- Apr 2021
- First submitted
- 14 Mar 2019
- Last updated
- 23 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of Haploidentical Natural Killer Cells and IL-15 Super Agonist ALT-803 in Human Immunodeficiency Virus (HIV)
- ClinicalTrials.gov ID
- NCT03899480
- Acronym / sponsor ID
- IDIM-2018-26587
- Conditions
- Hiv, HIV Infections, Immune Deficiency
- Keywords
- Suppressive Antiretroviral Therapy (ART)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 2 Apr 2019 (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 therapeutic study of related donor HLA-haploidentical NK-cell based therapy to determine if the treatment is safe and well-tolerated and if there is any measureable impact on virus reservoirs.
Detailed description
Human immunodeficiency virus (HIV) infection causes profound and often irreversible changes to the adaptive and innate immune system. In the absence of antiretroviral therapy (ART), Cluster of Differentiation (CD)4+ T cells are progressively depleted, CD8+ T cells are often expanded, and much of the immune system is chronically activated. Much of these abnormalities improve during long-term ART, but the system rarely returns to normal. Notably, chronic inflammation persists indefinitely during ART, and is driven by multiple factors, including HIV production (and perhaps replication), irreversible loss of the mucosal integrity and exposure to gut microbes, and an excess burden of other pathogens such as cytomegalovirus (CMV). How the virus and its host interact during effective ART is the focus of intense investigation.
HIV-1 preferentially infects activated memory CD4+ T cells that express the chemokine receptor CCR5, although resting CD4+ T cells, naïve CD4+ T cells and macrophages can also be infected. The majority of infected and activated CD4+ T cells die quickly, but a small fraction reverts to a resting state and persistent indefinitely as the latent reservoir. Because ART blocks all or nearly all new infection events, the reservoir that exists at the time ART is initiated becomes the reservoir that persists for the life of the individual. This memory T cell viral reservoir is maintained during ART by the long half-life of the infected cell, homeostatic proliferation of these cells and perhaps by low levels of persistent viral replication.
The viral reservoir in peripheral blood exists predominantly in those longer-lived memory CD4+ cells endowed with regenerative potential, including memory stem cells, central memory cells and transitional memory. The reservoir also persists in potentially shorter-lived CD4+ T effector cell populations, but whether these cells represent a stable reservoir or one that is constantly being regenerated via proliferation and differentiation is unknown.
"Shock and Kill". One approach to curing HIV infection that has generated broad support in the field is to induce latently infected cells to produce virus (the "shock") while enhancing the ability of the host to clear these virus-producing cells (the "kill"). Histone deacetylase (HDAC) inhibitors have been shown to increase production of HIV-1 RNA and to a lesser degree virus particles from the viral reservoir in vivo. The magnitude of the effect of HDAC inhibitors is modest at best, and as of yet this class of drugs has had no consistent effect on the frequency of cells that harbor replication-competent HIV. Other classes of anti-latency drugs and immunomodulators are therefore being explored for their capacity to stimulate the viral reservoir.
To augment the capacity of the host to eliminate reservoir cells following activation, several immunologic strategies are being explored. These strategies include therapeutic vaccines, monoclonal antibodies, and immune checkpoint inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Non-controlled intervention groups
| Arm | Type | Receives |
|---|---|---|
| Haploidentical Natural Killer Cells | Experimental | Biological: Haploidentical Natural Killer (NK) CellsDay -7 the subject will undergo inguinal lymph node biopsy \& colonoscopy to obtain ileal \& rectal biopsies. Blood samples will be obtained. PBMCs will be obtained to sort into CD4 subsets \& measure frequencies of HIV RNA \& DNA. On Day -1, the donor will undergo apheresis \& donor cells will be obtained \& incubated overnight. On Day 0 subjects will be infused with N-803 activated NK cells. Subjects will receive 1st dose of N-803 4 hrs after the infusion. Plasma will be obtained at 2, 4 \& 12 hrs after. Subjects will return on Days 2, 4, 7, 10, \& 14 for blood draw. Subjects will return Days 21 \& 42 for blood work \& to receive 2 additional doses of N-803, for a total of 3 doses. Subjects will be monitored for toxicity assessment by targeted physical exam \& laboratory evaluations on Days 2, 4, 7, 10, 21, \& 42. On day 49, we will perform lymph node biopsy \& colonoscopy to obtain ileal \& rectal tissues. The patient will then be followed until day 100 post infusion. |
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
- 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).
- Screening CD4 count ≥500 cells/µl
- Laboratory tests (Complete Blood Count, Comprehensive Metabolic Panel, Mg, Phosphorus, international normalized ratio/partial thromboplastin time (INR/PTT), Thyroid stimulating hormone (TSH)/T4,) performed within 14 days of infusion of donor NK cells. 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)
Key exclusion criteria (15 listed)
- Any condition that precludes leukapheresis, 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+).
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 |
|---|---|---|
| Haploidentical Natural Killer (NK) Cellsinfusion with N-803 activated NK cells | Biological | Haploidentical Natural Killer Cells |
Primary outcome
Adverse Events
Time frame: throughout trial participation: 100 days post infusion
Toxicity and adverse events will be classified according to Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v2.0. Scale ranges from grade 0 to 4 with a grade of 0 indicating normal signs and symptoms and a grade of 4 indicating potentially life-threatening signs and symptoms. Grade 2, 3, and 4 adverse events will be considered when determining the safety and tolerability of treatment.
CBC; White Blood Cell Count
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. White blood cell count will be evaluated by principle investigator. WBC outside of established clinical reference range (4.5-11.0 k/ul) may indicate adverse treatment reaction. Total occurrence of abnormal CBC results will be used to determine treatment safety and tolerability.
CBC; Red Blood Cell Count
Time frame: 2, 3, 10, and 21 day post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Red blood cell count will be evaluated by principle investigator. RBC outside established clinical reference range (2.5-5.5 mil/ul) may indicate adverse treatment reaction. Total occurrence of abnormal CBC results will be used to determine treatment safety and tolerability.
CBC; Hemoglobin
Time frame: 2, 3, 10, and 21 days post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Hemoglobin will be evaluated by principle investigator. Hemoglobin outside established clinical reference range (14-17 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal hemoglobin results will be used to determine treatment safety and tolerability.
CBC; Hematocrit
Time frame: 2, 3, 10, and 21 days post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion. Hematocrit will be evaluated by principle investigator. Hematocrit outside established clinical reference range (42-52%) may indicate adverse treatment reaction. Total occurrence of abnormal hematocrit results will be used to determine treatment safety and tolerability.
CBC; Mean Corpuscular Volume
Time frame: 2, 3, 10, and 21 days post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCV will be evaluated by principle investigator. MCV outside established clinical reference range (84-96 fl.) may indicate adverse treatment reaction. Total occurrence of abnormal MCV results will be used to determine treatment safety and tolerability.
CBC; Mean Corpuscular Hemoglobin
Time frame: 2, 3, 10, and 21 days post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCH will be evaluated by principle investigator. MCH outside established clinical reference range (28-34 pg) may indicate adverse treatment reaction. Total occurrence of abnormal MCH results will be used to determine treatment safety and tolerability.
CBC; Mean Corpuscular Hemoglobin Concentration
Time frame: 2, 3, 10, and 21 days post infusion
Complete blood count will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. MCHC will be evaluated by principle investigator. MCHC outside established clinical reference range (33-36 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal MCHC results will be used to determine treatment safety and tolerability.
CMP; Sodium
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Sodium concentration will be evaluated by principle investigator. Sodium concentration outside established clinical reference range (136-145 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal sodium concentration results will be used to determine treatment safety and tolerability.
CMP; Potassium
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Potassium concentration will be evaluated by principle investigator. Potassium concentration outside established clinical reference range (3.5-5.1 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal potassium concentration results will be used to determine treatment safety and tolerability.
CMP; Chloride
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Chloride concentration will be evaluated by principle investigator. Chloride concentration outside established clinical reference range (98-107 mmol/l) may indicate adverse treatment reaction. Total occurrence of abnormal chloride concentration results will be used to determine treatment safety and tolerability.
CMP; Glucose
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Glucose concentration will be evaluated by principle investigator. Glucose concentration outside established clinical reference range (70-99 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal glucose concentration results will be used to determine treatment safety and tolerability.
CMP; Calcium
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Calcium concentration will be evaluated by principle investigator. Calcium concentration outside established clinical reference range (8.2-10.2 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal calcium concentration results will be used to determine treatment safety and tolerability.
CMP; Blood Urea Nitrogen
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. BUN concentration will be evaluated by principle investigator. BUN concentration outside established clinical reference range (6-25 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal BUN concentration results will be used to determine treatment safety and tolerability.
CMP; Creatinine
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Creatinine concentration will be evaluated by principle investigator. Creatinine concentration outside established clinical reference range (0.8-1.3 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal creatinine concentration results will be used to determine treatment safety and tolerability.
CMP; Alkaline Phosphatase
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Alkaline phosphatase concentration will be evaluated by principle investigator. Alkaline phosphatase concentration outside established clinical reference range (26-137 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal alkaline phosphatase concentration results will be used to determine treatment safety and tolerability.
CMP; Alanine Transaminase
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Alanine transaminase concentration will be evaluated by principle investigator. Alanine transaminase concentration outside established clinical reference range (15-65 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal alanine transaminase concentration results will be used to determine treatment safety and tolerability.
CMP; Aspartate Transaminase
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Aspartate transaminase concentration will be evaluated by principle investigator. Aspartate transaminase concentration outside established clinical reference range (0-37 u/l) may indicate adverse treatment reaction. Total occurrence of abnormal aspartate transaminase concentration results will be used to determine treatment safety and tolerability.
CMP; Total Bilirubin
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Total bilirubin concentration will be evaluated by principle investigator. Total bilirubin concentration outside established clinical reference range (<1.1 mg/dl) may indicate adverse treatment reaction. Total occurrence of abnormal total bilirubin concentration results will be used to determine treatment safety and tolerability.
CMP; Albumin
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Serum albumin will be evaluated by principle investigator. Serum albumin concentration outside established clinical reference range (3.2-4.7 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal serum albumin concentration results will be used to determine treatment safety and tolerability.
CMP; Total Protein
Time frame: 2, 3, 10, and 21 days post infusion
Comprehensive metabolic panel will be performed at days 2, 3, 10, 21 post infusion to aid in the continuous assessment of safety and tolerability throughout the study. Total protein will be evaluated by principle investigator. Total protein concentration outside established clinical reference range (6.4-8.2 g/dl) may indicate adverse treatment reaction. Total occurrence of abnormal total protein concentration results will be used to determine treatment safety and tolerability.
1 secondary outcome
Decrease in HIV reservoirs
Time frame: 100 days post infusion
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 23 Apr 2021.
- 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.
- 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.
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 Haploidentical Natural Killer (NK) Cells in people with Hiv and HIV Infections, 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 23 Apr 2021. 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?
Adverse Events (time frame: throughout trial participation: 100 days post infusion). The study lists 21 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 NCT03899480, 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 23 Apr 2021.