Adoptive Transfer of Haploidentical Natural Killer Cells and IL-2

NCT03346499 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 1508M77601-2
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Keywords

HIV

Outcome Measures

Primary Outcomes (2)

• 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

  Baseline, 100 days

• Tolerability of administration of haploidentical NK cells in HIV infected individuals- Side effects

  Side effects from all subjects will be collected

  Baseline, 100 days

Study Arms (1)

NK cells and IL-2

EXPERIMENTAL

Biological: NK cells and IL-2

Interventions

NK cells and IL-2 BIOLOGICAL

Natural Killer Cells

NK cells and IL-2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ¥ 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 38207119 DERIVED

MeSH Terms

Interventions

Interleukin-2

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Timothy Schacker, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: November 17, 2017
• Study Start: March 9, 2017
• Primary Completion: November 13, 2018
• Study Completion: November 13, 2018
• Last Updated: November 20, 2019

Record last verified: 2019-11

Locations

US (1)