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

Primary Purpose

Epstein-Barr Virus Infections, Adenovirus, Cytomegalovirus Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cytotoxic T Lymphocytes
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Epstein-Barr Virus Infections focused on measuring Cytoxic T Lymphocytes(CTL), T-cell Depleted, Allogeneic Transplant, Epstein Barr Virus, Adenovirus, Cytomegalovirus, Hematopoietic progenitor cell transplantation

Eligibility Criteria

undefined - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Multi-Virus CTLs

Arm Description

The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study.

Outcomes

Primary Outcome Measures

To assess toxicity by SAEs scored according to the adaptive CTCAE version 5
Phase/safety/toxicity

Secondary Outcome Measures

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

Full Information

First Posted
February 6, 2012
Last Updated
October 21, 2021
Sponsor
Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT01535885
Brief Title
Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV
Acronym
ACE
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
October 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Infections, Adenovirus, Cytomegalovirus Infections
Keywords
Cytoxic T Lymphocytes(CTL), T-cell Depleted, Allogeneic Transplant, Epstein Barr Virus, Adenovirus, Cytomegalovirus, Hematopoietic progenitor cell transplantation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Multi-Virus CTLs
Arm Type
Experimental
Arm Description
The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study.
Intervention Type
Biological
Intervention Name(s)
Cytotoxic T Lymphocytes
Intervention Description
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.
Primary Outcome Measure Information:
Title
To assess toxicity by SAEs scored according to the adaptive CTCAE version 5
Description
Phase/safety/toxicity
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs
Description
Immunity will be recorded.
Time Frame
1 year
Title
The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant
Description
Number of infections will be quantified.
Time Frame
1 year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie-An Talano, MD
Organizational Affiliation
Medical College of Wisconsin/Children's Hospital of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

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

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