Donor-Derived Viral Specific T-cells (VSTs)

Viral Infection Clinical Trial

— VSTs  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02048332
• Other study ID #: 2013-2777
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 5, 2014
• Est. completion date: January 2027

Study information

• Verified date: March 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Jamie Wilhelm, BS
• Phone: (513) 803-1102
• Email: Jamie.Wilhelm[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: January 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Weeks and older

Eligibility

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

Related Conditions & MeSH terms

• Allogeneic Stem Cell Transplant
• Infections
• Viral Infection
• Viral Reactivation
• Virus Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Hoxworth Blood Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of patients who do not have infusional toxicity	Patients will be monitored for infusional toxicity	Through 30 minutes post infusion
Primary	Incidence of GVHD associated with VST infusion	Patients will be monitored for the development of VST associated GVHD	Through 30 days after infusion
Secondary	Presence of viral-specific T-cells	Presence of viral-specific T-cells in the participant's blood will be assessed by Elispot assay	At 30 days after infusion
Secondary	Viral burden	The viral burden will be assessed using the protocol-defined efficacy assessment	At 30 days after infusion