Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against Epstein Barr Virus, Adenovirus, And Cytomegalovirus - Full Text View

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:

MedlinePlus related topics: Cytomegalovirus Infections

Drug Information available for: Herpesvirus 4, Human

Genetic and Rare Diseases Information Center resources: Cytomegalic Inclusion Disease

U.S. FDA Resources

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:

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 Epstein-Barr Virus Infections DNA Virus Infections Herpesviridae Infections	Neoplasms Neoplasms, Experimental Tumor Virus Infections Virus Diseases

ClinicalTrials.gov processed this record on March 03, 2015

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