Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Allogeneic Stell Cell Transplant, Viral Infection

Intervention / Treatment
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* Biological: Viral Specific T-cells (VSTs) Scheduled
* Biological: Viral Specific T-cells (VSTs) Treatment


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VSTs to Prevent<br>VSTs are given through an IV infusion 21 days after transplant to see if the VSTs will help prevent a viral infection. | Biological: Viral Specific T-cells (VSTs) Scheduled<br>* VSTs will be infused into stem cell transplant recipients on schedule.<br>|
| Experimental: VSTs to Treat<br>VSTs will be given only if a viral infection develops. | Biological: Viral Specific T-cells (VSTs) Treatment<br>* VSTs will be infused into stem cell transplant recipients only if viremia is detected.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 21 - 100 days after transplant |