Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation

NCT03475212 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PBMTC SUP1701
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 30

Brief Summary

The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

Conditions

Cytomegalovirus Infections; Adenovirus Infection; EBV Infection

Keywords

Hematopoietic Stem Cell Transplant; Primary Immune Deficiency Disease

Outcome Measures

Primary Outcomes (3)

• Feasibility to identify suitable HLA matched VST products

  Feasibility will be defined as the ability of the investigators to identify suitable partially HLA- matched VST products from the VST bank at Children's National Medical Center for referred study subjects. The percentage of referred patients with potential partially-matched VST products identified will be recorded, as will timing between patient referral and treatment.

  30 days

• Incidence of Treatment-Emergent Adverse Events

  The safety endpoint, dose-limiting toxicity (DLT), will be defined as acute GvHD grades III-IV or grades 3-5 infusion-related adverse events or grades 4-5 non-hematological adverse events related to the T cell product within 30 days of each VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.

  30 days

• Efficacy of VST at 30 days as measured by viral load

  Peripheral blood and, where relevant, stool and urine will be monitored for CMV, EBV, and/or adenovirus viral load. For patients with multiple viral infections, the response against the primary viral target will determine the classification. For the infection under treatment response in viral load will be assessed at 30 days after the first VST infusion

  30 days

Secondary Outcomes (4)

• Reconstitution of Antiviral Immunity following VST infusions

  3 months

• Persistence of infused VSTs

  1 month and 3 months

• Effects on Clinical Signs of Viral Infection

  3 months

• Survival

  6 months and 12 months

Study Arms (1)

Virus specific T cell lines (VSTs) against three viruses

EXPERIMENTAL

The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.

Biological: Virus Specific T-cell (VST) infusion

Interventions

Virus Specific T-cell (VST) infusion BIOLOGICAL

Patients will receive partially HLA-matched VSTs as a single infusion. Patients who have a partial response (\>1 log decrease in viral load without clearance) or no response and do not have treatment-related dose-limiting toxicities are eligible to receive up to 3 additional doses from day 30 after the initial infusion and at 2 weekly intervals thereafter. The viral load of the virus (or viruses) that patients are initially treated for are monitored by viral PCR.

Virus specific T cell lines (VSTs) against three viruses

Eligibility Criteria

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

You may qualify if:

• Patients who have received any type of allogeneic transplant or who have a primary immunodeficiency disorder will be eligible if they have CMV, adenovirus, and/or EBV infection/disease with failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy.
• Patients must meet one of the following criteria:
• Recipient of prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cell or single or double cord blood within the previous 18 months, OR
• Have a diagnosed primary immunodeficiency disorder (as defined by clinical and laboratory evaluations) and not undergone HSCT.
• Treatment of the following persistent or relapsed infections despite standard therapy:
• CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy. For CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir for at least 14 days.
• Adenovirus: Treatment of persistent or relapsed adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or brincidofovir.
• EBV: Treatment of persistent or relapsed EBV infection despite standard therapy.
• For EBV infection, standard therapy is defined as rituximab given at 375 mg/m2 in patients for 1-4 doses with a CD20+ tumor.
• Patients with simultaneous infections with CMV, EBV and/or Adenovirus infections are eligible if one or more infection(s) is persistent or relapsed despite standard therapy as defined above. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
• Clinical status at enrollment that allows tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent) prior to infusion of the VST doses.
• Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
• Written informed consent and/or signed assent line from patient, parent or guardian.

You may not qualify if:

• Patients receiving ATG, Campath, Basiliximab or other immunosuppressive monoclonal antibodies targeting T-cells within 28 days of screening for enrollment.
• Patients who have received donor lymphocyte infusion (DLI) or other experimental cellular therapies within 28 days.
• Current therapy with ruxolitinib or other JAK inhibitors within the previous 3 days.
• Patients with other uncontrolled infections, defined as bacterial or fungal infections with clinical signs of worsening despite standard therapy. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients 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, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients with active and uncontrolled relapse of malignancy (if applicable).

Sponsors & Collaborators

• Pediatric Transplantation & Cellular Therapy Consortium: lead

Study Sites (30)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 91016, United States

Location

Stanford Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

UCSF Medical Center

San Francisco, California, 94123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Yale

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center

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

Location

Emory University/Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, 46202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute/ Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Spectrum Health - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Jude

Memphis, Tennessee, 38105, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Children's Mercy

San Antonio, Texas, 78229, United States

Location

Methodist Healthcare System of San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center/Seattle Chlindren's/University of Washington School of Medicine

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections; Adenoviridae Infections; Epstein-Barr Virus Infections; Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Michael Pulsipher, MD

  Children's Hospital Los Angeles

  STUDY CHAIR

• Michael Keller, MD

  Children's National Research Institute

  STUDY CHAIR

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: Sponsor-Investigator, Protocol Co-Chair

Study Record Dates

• First Submitted: January 13, 2018
• First Posted: March 23, 2018
• Study Start: June 20, 2018
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: May 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)