Donor-Derived Viral Specific T-cells (VSTs)

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Recruiting

CT.gov ID

NCT02048332

Collaborator

Hoxworth Blood Center (Other)

450

Enrollment

Location

Arm

154.8

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Allogeneic Stem Cell Transplant Viral Infection Viral Reactivation	Biological: Viral specific VST Infusion	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 5, 2014

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Successful production of viral specific T-cells [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.
Percentage of patients who do not have infusional toxicity [Through 30 minutes post infusion]
Patients will be monitored for infusional toxicity
Incidence of GVHD associated with VST infusion [Through 30 days after infusion]
Patients will be monitored for the development of VST associated GVHD

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Weeks and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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