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

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)

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.

Study Overview

• Status: Completed
• Conditions: Epstein-Barr Virus Infections; Cytomegalovirus Infections; Adenovirus
• Intervention / Treatment: Biological: Cytotoxic T Lymphocytes

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Multi-Virus CTLs; The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study.	Biological: Cytotoxic T Lymphocytes; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Julie-An Talano, MD, Medical College of Wisconsin/Children's Hospital of Wisconsin

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): October 1, 2019
• Study Completion (ACTUAL): October 1, 2019

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 15, 2012
• First Posted (ESTIMATE): February 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Cytomegalovirus; Epstein Barr Virus; Adenovirus; Allogeneic Transplant; Cytoxic T Lymphocytes(CTL); T-cell Depleted; Hematopoietic progenitor cell transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Adenoviridae Infections
• Other Study ID Numbers: CTL-11/157