Administration of Virus-Specific Cytotoxic T-Lymphocytes

NCT00590083 | Completed Phase 1 DMC

• 1 other identifier: 14097-LYPTAIST
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

The main purpose of this study is to see if these T-lymphocytes are safe. To make these Ad-specific T lymphocytes the investigators will obtain blood from the stem cell donor and transfer Ad into another type of blood cell, called monocytes. These cells can then stimulate the T lymphocytes and train them to kill cells infected with Ad. The investigators will then grow these Ad-specific T lymphocytes by more stimulation with Ad-infected monocytes and a third type of blood cell called a B lymphoblast from the donor. After testing the T -lymphocytes, the investigators will inject them into patients after transplant who are at high risk of serious Ad virus infection. The investigators will make sure the injected cells are safe and see if they affect the growth and behavior of adenoviruses in the patient's own body.

Conditions

Adenovirus Infection

Keywords

stem cell transplantation; adenovirus; Cytotoxic T-Lymphocytes; prophylaxis

Outcome Measures

Primary Outcomes (3)

• safety, toxicity and MTD of 1 IV injection of donor-derived adenovirus-specific CTLs given as adenovirus prophylaxis to patients at risk of developing adenovirus infection after allogeneic stem cell transplant.

  1 year

• To evaluate the recovery of virus-specific immunity after CTL infusion and assess its correlation with protection from viral load and disease.

  1 year

• To obtain preliminary information regarding whether the presence of antigen is required for Ad-specific CTL persistence in vivo.

  1 year

Study Arms (1)

Virus Specific Cytoxic T lymphocytes

EXPERIMENTAL

Virus Specific Cytoxic T lymphocytes

Biological: CTL administration

Interventions

CTL administration BIOLOGICAL

Adenovirus specific T cells will be given by intravenous injection from day 30 post transplant. One infusion of Adenovirus-specific CTL given to patients at risk for Adenoviral disease after matched or mismatched unrelated or matched or mismatched related donor stem cell transplant. Four dose levels will be explored. The lowest level will be 1x dose of 5x10e6cells/m2 and the highest will be 1x dose of 1.35x10e8/m2.

Virus Specific Cytoxic T lymphocytes

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipients of allogeneic (i.e. HLA matched or mismatched related or unrelated) donor stem cell transplants at risk for Adenoviral disease
• No evidence of GVHD \> Grade II at time of enrollment
• Life expectancy \> 30 days
• No severe intercurrent infections
• Lansky/Karnofsky scores \>60
• Absence of severe renal disease (Creatinine \> x 3 normal for age)
• Absence of severe hepatic disease (direct bilirubin \> 3 mg/dl or SGOT \> 500)
• Patient must be at least 30 days post transplant to be eligible to receive CTL
• Not receiving Cidofovir
• Patient has not received other viral specific CTL prophylactically within 4 weeks of receiving Adv-CTL
• Patient/guardian able to give informed consent

You may not qualify if:

• Patients with GVHD Grades III-IV
• Patients with hepatic or renal disease as specific above
• Patient has received other viral specific CTL (e.g. EBV-specific CTL or CMV-specific CTL) within 4 weeks of receiving Adv-CTL
• Patients with Adenoviral disease prior to day +30 post transplant Adenoviral diseases defined as the presence of more than two sites positive for adenovirus by culture
• Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

National Institute of Health (NIH)

Washington D.C., District of Columbia, 20894, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, Kennedy-Nasser AA, Leung KS, Gee AP, Krance RA, Brenner MK, Heslop HE, Rooney CM, Bollard CM. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009 Nov 5;114(19):4283-92. doi: 10.1182/blood-2009-07-232454. Epub 2009 Aug 21.

  PMID: 19700662 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Catherine Bollard, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 10, 2008
• Study Start: July 1, 2003
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: February 19, 2014

Record last verified: 2014-02

Locations

US (3)