Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV

Study Overview
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Brief Summary
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This protocol is a phase I study. Patients may be eligible for an infusion of Multi-virus Cytotoxic T Lymphocytes (CTL) if they received a T-cell depleted (TCD) transplant from a related family member or an unrelated donor. Recipients of these types of transplants are severely immune compromised during the early post-transplant period and are more susceptible to certain viruses. The investigators hypothesize that the adoptive transfer of Cytotoxic T Lymphocytes (CTL) against certain viruses: Adenovirus, Cytomegalovirus and Epstein Barr Virus (Ad, CMV, and EBV) will be safe with regard to producing graft versus host disease (GVHD) or other infusion related toxicities.

Detailed Description
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Within this clinical trial, the investigators will test the hypotheses that the administration of CTLs for prophylaxis against Ad, CMV and EBV in recipients of TCD-HPCT will be safe and well tolerated. Graded doses of Multi-Virus CTL will be administered to recipients of genotypically haploidentical or mismatched unrelated TCD grafts.

Official Title
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A Phase I Study Of Using Multi-virus Cytotoxic T-cells Following T-cell Depleted Allogeneic Hematopoietic Progenitor Cell Transplantation For Prophylaxis Against Specific Pathogens- Epstein Barr Virus, Adenovirus, And Cytomegalovirus (ACE)

Conditions
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Epstein-Barr Virus Infections, Adenovirus, Cytomegalovirus Infections

Intervention / Treatment
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* Biological: Cytotoxic T Lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age < 22 years. Both genders and all races are eligible. The patient population chosen for the T-cell depleted allogeneic HPCT from a related or unrelated allogeneic donor must meet eligibility based on institutional SOPs and/or the IRB approved T cell depleted allogeneic HPCT protocol which they are enrolled. Must be willing to sign a written informed consent. Patient Organ Status at the time of enrollment (pre-transplant) Lansky or Karnofsky score > 50 Echocardiogram shortening fraction > 27% Renal function: serum creatinine < 2 x normal for age DLCO > 50% predicted in patients old enough to comply with PFTs or no baseline oxygen requirement for younger patients. Hepatic: AST, ALT < 5x upper limit of normal; bilirubin < 2.0 mg/dl Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months following CTL infusion. The male partner should use a condom. Patients must be between 28 and 100 days post T-cell depleted allogeneic HPCT Patients must meet the following criteria (within 72 hours of CTL infusion): Achieved primary engraftment with an ANC of at least 1000 per μl for 3 consecutive days. No oxygen requirement with oxygen saturations > 90%. AST, ALT < 5x upper limit of normal for age; bilirubin < 2 mg/dl. Hemoglobin > 8 gm/dl prior to infusion. (May be transfusion dependent). Renal function: serum creatinine < 2 x normal for age. The Patient must not have the following conditions on the day of CTL infusion: Exhibit overt hematologic manifestations of relapse or persistent disease. Evidence of recurrent/persistent disease based primarily on flow cytometry, cytogenetics, chimerism analysis, or other molecular studies does not by itself represent grounds for exclusion. Exclusion Criteria: Currently enrolled on another Phase I clinical trial. Pregnant or nursing Overt hematologic manifestations of relapse or persistent disease Having > grade 1 graft-versus-host disease.

Ages Eligible for Study
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Maximum Age: 22 Years

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-Virus CTLs<br>The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study. | Biological: Cytotoxic T Lymphocytes<br>* Patients will be studied in cohorts of 3. Eligible patients will receive a single Multi-Virus CTL line infusion 28-100 days after their transplant. The dose will start at dose level 1 (2.0 x 106/kg). After each cohort of 3 patients has been treated at each of the dose levels, decisions will be made if the next high or lower dose level should be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess toxicity by SAEs scored according to the adaptive CTCAE version 5 | Phase/safety/toxicity | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs | Immunity will be recorded. | 1 year | 
| The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant | Number of infections will be quantified. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytoxic T Lymphocytes(CTL), T-cell Depleted, Allogeneic Transplant, Epstein Barr Virus, Adenovirus, Cytomegalovirus, Hematopoietic progenitor cell transplantation