Donor-Derived Viral Specific T-cells (VSTs)

NCT02048332 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2013-2777
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 3

Brief Summary

In this research study, the investigators want to learn more about the use of donor-derived viral specific T-cells (VSTs) to treat viral infections that occur after allogeneic stem cell transplant. A viral specific T cell is a T lymphocyte (a type of white blood cell) that kills cells that are infected (particularly with viruses). Allogeneic means the stem cells come from another person. These VSTs are cells specially designed to fight the virus infections that can happen after a bone marrow transplant. The investigators are asking people who have undergone or will undergo an allogeneic stem cell transplant to enroll in this research study, because viral infections are a common problem after allogeneic stem cell transplant and can cause significant complications including death. Stem cell transplant reduces a person's ability to fight infections. There is an increased risk of getting new viral infections or reactivation of viral infections that the patient has had in the past, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), BK virus (BKV), and JC virus. There are anti-viral medicines available to treat these infections, though not all patients will respond to the standard treatments. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find an easier way to treat these infections.

Conditions

Viral Reactivation; Allogeneic Stem Cell Transplant; Viral Infection

Keywords

Epstein-Barr Virus (EBV); Adenovirus (ADV); t-cells; donor; transplant; children; cytomegalovirus (CMV); BK virus (BKV)

Outcome Measures

Primary Outcomes (3)

• Successful production of viral specific T-cells

  Of the patients who had a VST culture initiated, successful production of VST cells is defined as meeting the protocol-defined release criteria.

  Within 30 days post culture initiation

• Percentage of patients who do not have infusional toxicity

  Patients will be monitored for infusional toxicity

  Through 30 minutes post infusion

• Incidence of GVHD associated with VST infusion

  Patients will be monitored for the development of VST associated GVHD

  Through 30 days after infusion

Secondary Outcomes (2)

• Presence of viral-specific T-cells

  At 30 days after infusion

• Viral burden

  At 30 days after infusion

Study Arms (1)

Viral Specific VST Infusion

EXPERIMENTAL

Viral reactivation or infection. VST Reinfusion required.

Biological: Viral specific VST Infusion

Interventions

Viral specific VST Infusion BIOLOGICAL

VSTs will be infused into stem cell transplant recipients who have evidence of viral infection or reactivation defined as any of the below: * Blood adenovirus PCR ≥ 1,000 * Blood CMV PCR ≥ 500 * Blood EBV PCR ≥ 9,000 * Plasma BKV PCR \>1,000 * Plasma JC Virus PCR \>1,000 * Evidence of invasive adenovirus infection or disease, defined as the presence of adenoviral positivity in one or more sites. * Evidence of invasive CMV infection, eg pneumonitis, retinitis, colitis * Evidence of invasive EBV disease/infection, EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation, or EBV-associated malignancies. * Evidence of symptomatic BK virus infection, which may include symptomatic hemorrhagic cystitis, or BK nephropathy. * Evidence of PML or other CNS infection due to JC virus.

Viral Specific VST Infusion

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient must be at least 21 days after stem cell infusion
• Clinical status must allow tapering of steroids to 0.5mg/kg prednisone or other steroid equivalent
• Recipient must have achieved engraftment with ANC ≥ 500

You may not qualify if:

• Active acute GVHD grades II-IV
• Uncontrolled bacterial or fungal infection
• Uncontrolled relapse of malignancy requiring treatment with chemotherapy
• Infusion of ATG or alemtuzumab within 2 weeks of VST infusion

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Hoxworth Blood Center: collaborator

Study Sites (3)

Akron Children's Hospital

Akron, Ohio, 44308, United States

RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

COMPLETED

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Related Publications (2)

• Galletta TJ, Lane A, Lutzko C, Leemhuis T, Cancelas JA, Khoury R, Wang YM, Hanley PJ, Keller MD, Bollard CM, Davies SM, Grimley MS, Rubinstein JD. Third-Party and Patient-Specific Donor-Derived Virus-Specific T Cells Demonstrate Similar Efficacy and Safety for Management of Viral Infections after Hematopoietic Stem Cell Transplantation in Children and Young Adults. Transplant Cell Ther. 2023 May;29(5):305-310. doi: 10.1016/j.jtct.2023.01.027. Epub 2023 Feb 3.

  PMID: 36736781 DERIVED

• Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, Jodele S, Thomas S, Cancelas JA, Bollard CM, Hanley PJ, Keller MD, Grimley O, Clark D, Clark T, Lindestam Arlehamn CS, Sette A, Davies SM, Nelson AS, Grimley MS, Lutzko C. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456.

  PMID: 34473237 DERIVED

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

• Michael Grimley, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jamie Wilhelm, BS

CONTACT

(513) 803-1102; Jamie.Wilhelm@cchmc.org

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: January 27, 2014
• First Posted: January 29, 2014
• Study Start: February 5, 2014
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (3)