Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant
Primary Purpose
Allogeneic Stell Cell Transplant, Viral Infection
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Viral Specific T-cells (VSTs) Scheduled
Viral Specific T-cells (VSTs) Treatment
Sponsored by
About this trial
This is an interventional other trial for Allogeneic Stell Cell Transplant
Eligibility Criteria
SCHEDULED ARM:
Inclusion Criteria:
- Recipient must be at least 21 days after stem cell infusion
- Clinical status must allow tapering of any steroids to < 0.5mg/kg prednisone or other steroid equivalent
- No critical illness making VST infusion hazardous
Exclusion Criteria:
- Active acute GVHD grades II-IV.
- Uncontrolled relapse of malignancy.
- Infusion of ATG or alemtuzumab within 2 weeks prior to VST infusion. Alemtuzumab levels will be collected in the second week following stem cell infusion in patients who received alemtuzumab as part of their conditioning regimen. The level must be less than or equal to 0.15 prior to infusion of VSTs. In patients with level greater than 0.15, alemtuzumab levels can be checked serially until a level ≤ 0.15 is obtained. They would become eligible for scheduled VST infusion at that point.
TREATMENT ARM
Inclusion Criteria:
- Blood adenovirus PCR ≥1,000
- Blood CMV PCR ≥ 500
- Blood EBV PCR ≥ 9,000
- Plasma BKV PCR >1,000
- Evidence of invasive adenovirus infection. Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from one site such as stool or blood or urine or nasopharynx. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture or PCR from more than 2 sites such as stool or blood or urine or nasopharynx.
- Evidence of invasive CMV infection, defined as pneumonitis, retinitis, colitis, hepatitis
- 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.
- Evidence of symptomatic BK virus infection, defined as hemorrhagic cystitis or BK nephropathy.
- No active acute GVHD grades II-IV
- No uncontrolled relapse of malignancy
- No infusion of ATG or alemtuzumab within 2 weeks of VST infusion.
- Clinical status must allow tapering of any steroids to < 0.5mg/kg prednisone or other steroid equivalent
Sites / Locations
- Cincinnati Children's Hospital Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
VSTs to Prevent
VSTs to Treat
Arm Description
VSTs are given through an IV infusion 21 days after transplant to see if the VSTs will help prevent a viral infection.
VSTs will be given only if a viral infection develops.
Outcomes
Primary Outcome Measures
Number of Treatment Failures
Treatment failure is defined as EBV>100,000, BKV >100,000, CMV >5,000 or Adv >50,000 at any time post randomization.
Secondary Outcome Measures
Full Information
NCT ID
NCT04230356
First Posted
January 13, 2020
Last Updated
February 22, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Hoxworth Blood Center
1. Study Identification
Unique Protocol Identification Number
NCT04230356
Brief Title
Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant
Official Title
A Randomized Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells (VSTs) for Control of Viral Infections After Allogeneic Stem Cell Transplant
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2021 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Hoxworth Blood Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research study is to learn more about the use of viral specific T-lymphocytes (VSTs) to prevent or treat viral infections that may happen after allogeneic stem cell transplant. Allogeneic means the stem cells come from another person. VSTs are cells specially designed to fight viral infections that may happen after a stem cell transplant (SCT).
Stem cell transplant reduces the body's ability to fight infections. Viral infections are a common problem after transplant and can cause significant complications. 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 a better way to treat these infections.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Stell Cell Transplant, Viral Infection
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VSTs to Prevent
Arm Type
Experimental
Arm Description
VSTs are given through an IV infusion 21 days after transplant to see if the VSTs will help prevent a viral infection.
Arm Title
VSTs to Treat
Arm Type
Experimental
Arm Description
VSTs will be given only if a viral infection develops.
Intervention Type
Biological
Intervention Name(s)
Viral Specific T-cells (VSTs) Scheduled
Intervention Description
VSTs will be infused into stem cell transplant recipients on schedule.
Intervention Type
Biological
Intervention Name(s)
Viral Specific T-cells (VSTs) Treatment
Intervention Description
VSTs will be infused into stem cell transplant recipients only if viremia is detected.
Primary Outcome Measure Information:
Title
Number of Treatment Failures
Description
Treatment failure is defined as EBV>100,000, BKV >100,000, CMV >5,000 or Adv >50,000 at any time post randomization.
Time Frame
21 - 100 days after transplant
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
SCHEDULED ARM:
Inclusion Criteria:
Recipient must be at least 21 days after stem cell infusion
Clinical status must allow tapering of any steroids to < 0.5mg/kg prednisone or other steroid equivalent
No critical illness making VST infusion hazardous
Exclusion Criteria:
Active acute GVHD grades II-IV.
Uncontrolled relapse of malignancy.
Infusion of ATG or alemtuzumab within 2 weeks prior to VST infusion. Alemtuzumab levels will be collected in the second week following stem cell infusion in patients who received alemtuzumab as part of their conditioning regimen. The level must be less than or equal to 0.15 prior to infusion of VSTs. In patients with level greater than 0.15, alemtuzumab levels can be checked serially until a level ≤ 0.15 is obtained. They would become eligible for scheduled VST infusion at that point.
TREATMENT ARM
Inclusion Criteria:
Blood adenovirus PCR ≥1,000
Blood CMV PCR ≥ 500
Blood EBV PCR ≥ 9,000
Plasma BKV PCR >1,000
Evidence of invasive adenovirus infection. Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from one site such as stool or blood or urine or nasopharynx. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture or PCR from more than 2 sites such as stool or blood or urine or nasopharynx.
Evidence of invasive CMV infection, defined as pneumonitis, retinitis, colitis, hepatitis
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.
Evidence of symptomatic BK virus infection, defined as hemorrhagic cystitis or BK nephropathy.
No active acute GVHD grades II-IV
No uncontrolled relapse of malignancy
No infusion of ATG or alemtuzumab within 2 weeks of VST infusion.
Clinical status must allow tapering of any steroids to < 0.5mg/kg prednisone or other steroid equivalent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Celeste Dourson, MS
Phone
513-636-7679
Email
Celeste.Dourson@cchmc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Jamie Wilhelm, BS
Phone
513-803-1102
Email
Jamie.Wilhelm@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stella Davies, MBBS, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celeste Dourson, MS
Phone
513-636-7679
Email
Celeste.Dourson@cchmc.org
First Name & Middle Initial & Last Name & Degree
Stella Davies, MBBS, PhD
12. IPD Sharing Statement
Learn more about this trial
Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant
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