T-Lymphocytes for Prevention or Treatment of Viral Infections Following Hematopoietic Stem Cell Transplantation

NCT03180216 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00008637
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity against CMV, EBV, adenovirus, HHV6, BK virus, JC virus, and human parainfluenza-3 (HPIV3), derived from eligible HSCT donors. In this trial, we will utilize a rapid generation protocol for broad spectrum multivirus-specific T cells for infusion to recipients of allogeneic hematopoietic stem cell transplant (HSCT), who are at risk of developing EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3, or with PCR/culture confirmed active infection(s) of EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). These cells will be derived from HSCT donors, and the study agent will be assessed at each dose for evidence of dose-limiting toxicities (DLT). This study will have two arms: Arm A will include patients who receive prophylactic treatment, and Arm B will include patients who receive VSTs for one or more active infections with targeted viruses. Determination of the study arm will be determined by the patient's clinical status. Study arms will each be analyzed for safety endpoints and secondary endpoints.

Conditions

Viral Infections; Bone Marrow Transplant Infection

Outcome Measures

Primary Outcomes (2)

• Incidence of acute GvHD (grade III-IV)

  Number of patients with acute GvHD grades III-IV within 45 days of the last dose of VSTs

  Within 45 days of the last VSTs dose

• Incidence of adverse events as per CTCAE common criteria guidelines.

  2\) Grades 3-5 infusion-related adverse events within 45 days of the last dose of VSTs, or 3) Grades 4-5 non-hematological adverse events within 45 days of the last VSTs dose based on a standardized clinical assessment form.

  Within 45 days of the last VSTs dose

Secondary Outcomes (2)

• Antiviral response

  1 year

• Antiviral Immunity

  1 year

Study Arms (1)

Prophylactic and treatment

EXPERIMENTAL

Virus Specific T cells (VSTs) for prophylactic and treatment of active viral infection(s) after HSCT. 3 different dose levels starting with 1 x 10E7 /m2 (a T cell number more than an order of magnitude lower than that administered at the time of an unmanipulated marrow infusion), followed by 2 x 10E7/m2 and a final dose 5 x 10E7 VSTs/m2

Biological: Virus Specific T cells (VSTs)

Interventions

Virus Specific T cells (VSTs) BIOLOGICAL

This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity against CMV, EBV, adenovirus, HHV6, BK virus, JC virus, and human parainfluenza-3 (HPIV3), derived from eligible HSCT donors. In this trial, we will utilize a rapid generation protocol for broad spectrum multivirus-specific T cells for infusion to recipients of allogeneic hematopoietic stem cell transplant (HSCT), who are at risk of developing EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3, or with PCR/culture confirmed active infection(s) of EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). These cells will be derived from HSCT donors, and the study agent will be assessed at each dose for evidence of dose-limiting toxicities (DLT).

Prophylactic and treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells no earlier than 5 days prior to the date of VST infusion. VSTs administered as:
• Prophylaxis for patients at risk of EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3.
• Treatment of reactivation or active infection(s) with EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). Patients with multiple infections due to the targeted viruses are also eligible.
• Clinical status at infusion allows for tapering of steroids to less than 0.5 mg/kg/day prednisone or equivalent. 3) Karnofsky/Lansky score of ≥ 50.
• \) Bilirubin ≤ 2x, AST ≤5x, Serum creatinine ≤2x upper limit of normal, Hgb ≥8.0 g/dL (level can be achieved with transfusion).
• \) Pulse oximetry of \> 90% on room air. 6) Available multivirus-specific cytotoxic T lymphocytes 7) Negative pregnancy test (if female of childbearing potential). 8) Patient or parent/guardian capable of providing informed consent.

You may not qualify if:

• Patients with other uncontrolled infections.
• Patients who received ATG, Campath, Basiliximab or other T cell immunosuppressive monoclonal antibodies within 28 days prior to VST infusion.
• Received donor lymphocyte infusion or other cellular therapies (with the exception of allogeneic cells related to transplantation) within 28 days prior to VST infusion.
• Evidence of acute GVHD grades II-IV.
• Active and uncontrolled relapse of malignancy.
• Patients with Grade ≥ 3 hyperbilirubinemia.
• Patients who have received investigational (IND) product within 28 days prior VST infusion.

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Childrens National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (1)

• Harris KM, Horn SE, Grant ML, Lang H, Sani G, Jensen-Wachspress MA, Kankate VV, Datar A, Lazarski CA, Bollard CM, Keller MD. T-Cell Therapeutics Targeting Human Parainfluenza Virus 3 Are Broadly Epitope Specific and Are Cross Reactive With Human Parainfluenza Virus 1. Front Immunol. 2020 Oct 5;11:575977. doi: 10.3389/fimmu.2020.575977. eCollection 2020.

  PMID: 33123159 DERIVED

MeSH Terms

Conditions

Virus Diseases

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Michael D Keller, MD

  Children's National Research Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Allergy / Immunology

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: June 8, 2017
• Study Start: February 15, 2017
• Primary Completion: March 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)