Clinical trial NCT02048332: Donor-Derived Viral Specific T-cells (VSTs)
Official title: Donor-Derived Viral Specific T-cells (VSTs) for Treatment of Viral Infections After Allogeneic Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Allogeneic Stem Cell Transplant
Viral Infection
Viral Reactivation
Keywords: Epstein-Barr Virus (EBV)
Adenovirus (ADV)
t-cells
donor
transplant
children
cytomegalovirus (CMV)
BK virus (BKV)
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Hoxworth Blood Center
First posted: 2014-01-29
Enrollment: 750
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 requiring treatment with chemotherapy
* Infusion of ATG or alemtuzumab within 2 weeks of VST infusion

Primary outcomes:
measure: Successful production of viral specific T-cells
timeFrame: Within 30 days post culture initiation
measure: Percentage of patients who do not have infusional toxicity
timeFrame: Through 30 minutes post infusion
measure: Incidence of GVHD associated with VST infusion
timeFrame: Through 30 days after infusion
Secondary outcomes:
measure: Presence of viral-specific T-cells
timeFrame: At 30 days after infusion
measure: Viral burden
timeFrame: At 30 days after infusion
Other outcomes:
Locations:
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Michael Grimley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.