Donor-Derived Viral Specific T-cells (VSTs) (VSTs)

March 9, 2024 updated by: Children's Hospital Medical Center, Cincinnati

Donor-Derived Viral Specific T-cells (VSTs) for Treatment of Viral Infections After Allogeneic Stem Cell Transplant

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The stem cell matched donor will be asked to provide a blood donation for the VSTs generation. In the laboratory, the investigators will treat this blood sample to select out the cells that will help fight viruses. The cells will be grown with peptides (protein fragments that represent parts of the virus that will encourage the donor immune cells to grow). The cells will be grown in the laboratory so that there is a stock of virus fighting cells for the patient to use in the future. The investigators will freeze the cells and store them in a freezer in the laboratory.

If the patient has signs of virus in their blood after the transplant, they will be given the cells to help fight the infection. If there are signs that the cells are helping fight the infection, more cells may be given. The patient may get the cells up to 5 times, with 21 days between each treatment (this timeframe may be shortened to 14 days for patients with no evidence of viral response). If the patient does not show signs of a virus, the cells will stay in the freezer.

Following VST infusion, (s)he will be monitored with physical exams daily while inpatient and weekly while outpatient as well as blood tests weekly until 30 days after the last infusion of cells. The patient will have 3 teaspoons (15 mL) of blood drawn and urine collected before each cell infusion and then once a week after each infusion for 4 weeks and then once a month if possible for 1 year after the last infusion, all to monitor for the viral response.

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Akron Children's Hospital
        • Contact:
        • Principal Investigator:
          • Megan Sampson, MD
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Michael Grimley, MD
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
        • Principal Investigator:
          • Bryan Hambley, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 weeks and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Viral Specific VST Infusion
Viral reactivation or infection. VST Reinfusion required.
Biological: Viral specific VST Infusion

VSTs will be infused into stem cell transplant recipients who have evidence of viral infection or reactivation defined as any of the following:

  • 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Successful production of viral specific T-cells
Time Frame: Within 30 days post culture initiation
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
Time Frame: Through 30 minutes post infusion
Patients will be monitored for infusional toxicity
Through 30 minutes post infusion
Incidence of GVHD associated with VST infusion
Time Frame: Through 30 days after infusion
Patients will be monitored for the development of VST associated GVHD
Through 30 days after infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of viral-specific T-cells
Time Frame: At 30 days after infusion
Presence of viral-specific T-cells in the participant's blood will be assessed by Elispot assay
At 30 days after infusion
Viral burden
Time Frame: At 30 days after infusion
The viral burden will be assessed using the protocol-defined efficacy assessment
At 30 days after infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

Hoxworth Blood Center

Investigators

  • Principal Investigator: Michael Grimley, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2014

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

January 27, 2014

First Submitted That Met QC Criteria

January 27, 2014

First Posted (Estimated)

January 29, 2014

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 9, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-2777

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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