TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.

NCT04013802 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-44843 TETRAVI
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to use VSTs (virus-specific T cells) from a donor that is a partial HLA (human leukocyte antigen) match with the patient to treat viral infections after an allogeneic hematopoietic stem cell transplant (HSCT). These cells may also have value in CAR-T recipients who have received a product that depletes virus specific T cells. The patient must have had a myeloablative or non-myeloablative allogeneic HSCT using either bone marrow, single/double umbilical cord blood, or peripheral blood stem cells (PBSC) or CAR T cell product targeting an antigen expressed on virus specific T cells. After a transplant, while the immune system grows back, the patient is at risk for infection. Some viruses can stay in the body for life and are normally controlled by a healthy immune system, but if the immune system is weakened, like after a transplant, they can cause life threatening infections. He/she must have had an infection with one or more of the following viruses -Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus (AdV), Human polyomavirus type I (BKV), and human polyomavirus type II (JCV)- that has persisted or recurred despite standard therapy. In this study, the investigators want to use white blood cells that have been trained to treat viral infections. In an earlier study the investigators showed that treatment with such specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical for patients who already have an infection. In a subsequent study, the investigators were able to create multivirus-specific T cells (VSTs) from the blood of healthy donors and created a bank of these cells. The investigators then successfully used these banked cells to treat virus infections after a stem cell transplant. In this study the investigators have further modified their production method to decrease the potential side effects and the investigators want to find out if they can use these banked VSTs to fight infections caused by the viruses mentioned above.

Conditions

Viral Infection

Keywords

cytomegalovirus (CMV); BK virus; Epstein-Barr virus (EBV); adenovirus

Outcome Measures

Primary Outcomes (1)

• Treatment related adverse events.

  The primary objective is to measure the safety of MVSTs based on patients with grades 3-5 non-hematologic adverse events that are at least possibly related to the T cell product.

  28 days after the last dose of MVST

Secondary Outcomes (3)

• Number of patients with acute GvHD.

  42 days after the last dose of MVST

• Antiviral Response.

  42 days following the last treatment of MVST

• Number of patients with secondary graft failure.

  42 days following the last treatment of MVST

Study Arms (1)

HLA-matched VSTs

EXPERIMENTAL

Partially HLA-matched VSTs will be thawed and given by intravenous injection. Patients will receive 2 x 10\^7 or 4 x 10\^7 partially HLA-matched MVSTs, depending on their body surface area, as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused with agreement of the principal investigator, patient and/or guardian and the treatment team Additional doses may be from the same donor or a different donor based on available cell lines and patient/disease factors. Decision to switch to a different donor can be made by the principal investigator based on factors that include sequential treatment of different viral infections, concerns for immune escape of the targeted virus and/or availability of a better matched or otherwise superior VST line. Additional treatments will only be given following the agreement of the patient, treating physician, and investigator. This process can be repeated as needed.

Biological: HLA-matched VSTs

Interventions

HLA-matched VSTs BIOLOGICAL

An alternative approach that bypasses the need to grow VSTs for individual patients is to bank closely HLA-matched allogeneic VSTs that could be available as an "off the shelf" product. The HLA-matched VST product is to produce immune activity to CMV, Adv, BK virus and EBV in all recipients. Most recently our group extended this "off the shelf" approach to five viruses using the T cell product manufactured in 10 days. The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. A single infusion produced a cumulative complete or partial response rate of 92% overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (human herpesvirus) (n = 3).

HLA-matched VSTs

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 or single or double cord blood.
• Or Received CAR-T cells targeting an antigen expressed on normal virus specific T cells
• Treatment for Infection/Disease will fall into one of 3 categories (options):
• Option 1: Persistent, increasing or recurrent infections despite 7 days of standard therapy;
• a. 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, letermovir or cidofovir. 56, 57
• i. CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in broncheoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates or changes consistent with CMV retinitis on ophthalmologic examination.
• ii. CMV infection: defined as the presence of CMV positivity as detected by PCR or pp65 antigenemia or culture from ONE site such as stool or blood or urine or nasopharynx or bronchoalveolar lavage.
• b. Adenovirus: Treatment of persistent adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir.
• i. Adenovirus infection: defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or lung or nasopharynx.
• ii. Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, DFA or culture from two or more sites such as stool or blood or urine or lung or nasopharynx.
• c. EBV: For treatment of persistent EBV infection despite standard therapy. For EBV infection, standard therapy is defined as rituximab given at 375mg/m2 in patients for 1-4 doses with a CD20+ve tumor.58
• i. EBV infection: defined as: (1) Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR;
• ii. (2) Or clinical or imaging findings consistent with EBV lymphoma and/or elevated EBV viral load in peripheral blood.
• d. BK virus: Treatment of persistent BK virus infection or BK virus disease despite antiviral treatment with cidofovir or leflunomide. No clear standard treatment is defined (section 1.1.5). Cidofovir has been administered in low doses as well as high doses to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy.
• i. BK virus infection is defined as the presence of BK virus positivity as detected by PCR or culture in one site such as blood or urine or lung.

You may not qualify if:

• Patients receiving ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
• Patients with other uncontrolled infections. 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 attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients who are less than 28 days removed from their allogeneic hematopoietic stem cell transplant or who have received donor lymphocyte infusions (DLI) or CAR-T within 28 days.
• Patients with active acute GVHD grades II-IV.
• Uncontrolled relapse of malignancy
• Requirement for FiO2 \> 50% oxygen to maintain oxygen saturation \> 90% (peripheral pulse-ox). Note: patients requiring oxygen at FiO2\<=50% to maintain arterial oxygen saturation \>90% are eligible to receive MVSTs if the reason for this oxygen requirement is believed attributable to the virus being treated.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77003, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Virus Diseases; Epstein-Barr Virus Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Infections; Herpesviridae Infections; DNA Virus Infections; Tumor Virus Infections

Study Officials

• John Craddock, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Craddock, MD

CONTACT

832-824-1583; jacraddo@txch.org

Dustin McFadden

CONTACT

832-824-3855; Dustin.McFadden@bcm.edu

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: Associate Professor

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: March 8, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2031
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)