Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against Epstein Barr Virus, Adenovirus, And Cytomegalovirus (ACE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
Julie-An M. Talano, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01535885
First received: February 6, 2012
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Epstein-Barr Virus Infections
Adenovirus
Cytomegalovirus Infections
Biological: Cytotoxic T Lymphocytes
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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 TRIAL)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • To assess toxicity by SAEs scored according to the adaptive CTCAE version 4 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: February 2012
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Cytotoxic T Lymphocytes
    Patients will be studied in cohorts of 3. Eligible patients will receive a single Multi-Virus CTL line infusion 28-60 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.
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 2 allele mismatched relative) or mismatched unrelated TCD grafts.

  Eligibility

Ages Eligible for Study:   up to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age < 22 years.
  • Both genders and all races are eligible.
  • Undergoing a T-cell depleted allogeneic HPCT from a related HLA partially matched (two antigen mismatched, or haplodisparate) donor or a mismatched unrelated donor
  • 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 60 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535885

Contacts
Contact: Julie-An Talano, MD 414-955-4185 jtalano@mcw.edu
Contact: Kristine Allmendinger-Goertz, BA 414-266-2137 kallmend@mcw.edu

Locations
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie-An Talano, MD    414-955-4185      
Contact: Kristine Allmendinger-Goertz, BA    414-266-2137    kallmend@mcw.edu   
Principal Investigator: Julie-An Talano, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Julie-An Talano, MD Medical College of Wisconsin/Children's Hospital of Wisconsin
  More Information

No publications provided

Responsible Party: Julie-An M. Talano, Associate Professor of Pediatrics and Director of Clinical Pediatric BMT Research, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01535885     History of Changes
Other Study ID Numbers: CTL-11/157
Study First Received: February 6, 2012
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:
Cytoxic T Lymphocytes(CTL)
T-cell Depleted
Allogeneic Transplant
Epstein Barr Virus
Adenovirus
Cytomegalovirus
Hematopoietic progenitor cell transplantation

Additional relevant MeSH terms:
Adenoviridae Infections
Cytomegalovirus Infections
Virus Diseases
Epstein-Barr Virus Infections
DNA Virus Infections
Herpesviridae Infections
Tumor Virus Infections
Neoplasms, Experimental
Neoplasms

ClinicalTrials.gov processed this record on August 19, 2014