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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Epstein-Barr Virus Infections; Adenovirus; Cytomegalovirus Infections	Biological: Cytotoxic T Lymphocytes	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	18 participants
Intervention Model:	Single Group Assignment
Masking:	None (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)
Study Start Date :	February 2012
Estimated Primary Completion Date :	February 2019
Estimated Study Completion Date :	February 2019

Arms and Interventions

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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.

Outcome Measures

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Primary Outcome Measures :

1. To assess toxicity by SAEs scored according to the adaptive CTCAE version 4 [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs [ Time Frame: 1 year ]
2. The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant [ Time Frame: 1 year ]

Eligibility Criteria

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Ages Eligible for Study:	up to 22 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Julie-An Talano, MD	414-266-6471	jtalano@mcw.edu
Contact: Shelly LeVeque	414-266-6471	mleveque@chw.org

Locations

United States, Wisconsin
Medical College of Wisconsin	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Julie-An Talano, MD 414-266-6471
Contact: Shelly LeVeque 414-266-6471 mleveque@chw.org
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
First Posted:	February 20, 2012
Last Update Posted:	August 14, 2017
Last Verified:	August 2017

Keywords provided by Julie-An M. Talano, 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:

Infection; Communicable Diseases; Virus Diseases; Adenoviridae Infections; Cytomegalovirus Infections	Epstein-Barr Virus Infections; DNA Virus Infections; Herpesviridae Infections; Tumor Virus Infections