Evaluate the Safety, Immunologic, and Virologic Responses of Donor Derived (DD) HIV-Specific T-cells (HST) in HIV-infected Individuals Following Allogeneic Bone Marrow Transplantation (alloRESIST)

NCT04248192 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00012451
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-site phase 1 study of the safety, immunologic and virologic responses of ex vivo expanded donor-derived (DD) HIV-1 multi-antigen specific T-cell (HST) with non-escaped epitope targeting (NEET) therapy as a therapeutic strategy in HIV-infected individuals following Allogeneic Bone Marrow Transplantation (alloBMT).

Conditions

HIV-Infected Individuals

Outcome Measures

Primary Outcomes (1)

• Any ≥ Grade 3 Adverse Events (as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0)

  Any ≥ Grade 3 Adverse Events will be measured by number of participants who experience Dose Limiting Toxicity which is attributable to the DD HST-NEETS administration.

  45 days

Secondary Outcomes (2)

• The feasibility of manufacturing of DD HST-NEETs

  3 years

• The HIV reservoir measurements

  3 years

Study Arms (1)

Donor Derived HIV-Specific T-cells (DD HST-NEETs)

EXPERIMENTAL

Participants who meet specified inclusion criteria including neutrophil recovery post-transplant and for whom donor products have passed release testing will receive DD HST-NEETs at a dose of 2x107/m2 within 30 days of screening visit.

Biological: DD HST-NEETs

Interventions

DD HST-NEETs BIOLOGICAL

HIV-infected individuals following Allogeneic Bone Marrow Transplantation (alloBMT) will be treated with DD HST-NEETS therapy. Participants and donors will be screened for eligibility. Eligible donors will undergo a blood draw of up to 300mL to allow production of allogeneic DD HST-NEETs. Participants, who meet specified inclusion criteria including neutrophil recovery post-transplant and for whom donor products have passed release testing, will receive DD HST-NEETs at a dose of 2x107/m2 within 30 days of screening visit.

Donor Derived HIV-Specific T-cells (DD HST-NEETs)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Confirmation of HIV-1 infection. Any licensed ELISA test kit which is confirmed by Western blot or Multispot HIV-1/HIV-2 assay prior to screening. HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• On effective antiretroviral therapy.
• Ability and willingness of participant to continue and be compliant with ART throughout the study.
• Hematologic malignancy that qualifies for standard of care alloBMT according to JHU criteria.
• Potential participant must have adequate organ function for standard of care alloBMT according to JHU criteria.
• No active HCV infection. (If seropositive, participant must have no measureable HCV RNA within 30 days of enrollment).
• No active HBV infection (If seropositive, participant must have no measureable HBV DNA or HBsAg+ within 30 days of enrollment).
• Ability and willingness of participant to give written informed consent.
• Ability and willingness to communicate effectively with study personnel; considered reliable, willing, and cooperative in terms of compliance with the Protocol requirements.
• Ability and willingness to provide adequate locator information and contact information for at least 2 adults who can reach the participant within 24 hours
• Karnofsky score of ≥ 70.
• ANC ≥ 250/µL.
• Bilirubin ≤ 2x upper limit normal or direct bilirubin normal.
• AST ≤ 3x upper limit normal.

You may not qualify if:

• Participants receiving ATG, or Campath or other immunosuppressive T-cell monoclonal antibodies within 28 days.
• Participants with uncontrolled infections. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
• Participants who have received donor lymphocyte infusion (DLI) within 28 days.
• Active and uncontrolled relapse of malignancy.
• Participants with active acute GVHD grades II-IV
• Participants with bronchiolitis obliterans syndrome or serositis
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, pneumococcal polysaccharide) within 28 days prior to study entry.
• Inability to comply with study requirements, which could impact study integrity and/or safety.

Sponsors & Collaborators

• Catherine Bollard: lead

Study Sites (1)

Johns Hopkins University(Jhu)

Baltimore, Maryland, 21231, United States

Location

Study Officials

• Richard Ambinder, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Michael Keller, MD

  CNMC

  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 INVESTIGATOR
• PI Title: Director, Center for Cancer and Immunology Research

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: January 30, 2020
• Study Start: May 1, 2020
• Primary Completion: September 1, 2025
• Study Completion: April 1, 2026
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (1)