Safety, Toxicity and MTD of One Intravenous IV Injection of Donor CTLs Specific for CMV and Adenovirus — ACT-CAT  

Cytomegalovirus Infection Clinical Trial

Official title: Adoptive Transfer of Cord Blood T Cells To Prevent and Treat CMV and Adenovirus Infections After Transplantation

Status Completed

Clinical Trial Summary

With this study, we want to see if we can use a kind of white blood cell called T cells to prevent or treat AdV and CMV infection. We will grow these T cells from the cord blood before the patients transplant. These cells have been trained to attack adenovirus/CMV-infected cells and are called Adenoviral/CMV-specific cytotoxic (killer) T-cells or "AdV/CMV-CTL." We would plan to give the patient one dose of AdV/CMV-CTL any time from 30 days after their transplant. We have used T cells made in this way from the blood of donors to prevent infections in patients who are getting a bone marrow or blood stem cell transplant but this will be the first time we make them from cord blood.

Clinical Trial Description

We plan to grow T cells from the cord blood in the laboratory in a special way, to see if they can help prevent or treat infections in transplant patients with these viruses. This therapy with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from donor blood and given to patients receiving bone marrow or blood stem cell transplants. We want to find out if we can use CTLs that we will make from cord blood to prevent or treat viral infections when the patient's immunity is weak after receiving the cord blood transplant. These cells are called "CMV/AdV specific CTLs" because they can attack those two viruses.

The doctor will already have found a cord blood unit that is suitable for the patient's transplant. If the patient agrees to this study we will take 5-10 ml (1-2 teaspoons) from this cord blood unit before the transplant. We will only take as much cord blood as is available in a specially frozen small fraction of the cord blood unit.

We will use this cord blood to grow T cells in the lab. From this blood we will first grow special type of cells called dendritic cells and we will put a specially produced human virus (adenovirus) that carries the CMVpp65 gene into these dendritic cells. The dendritic cells will be irradiated so they cannot grow and then used to stimulate the T cells. This stimulation will train the T cells to kill cells with CMV and adenovirus on their surface.

We will then grow large numbers of these AdV/CMV-specific CTLs by more stimulation with EBV infected B cells (which we will make from the cord blood by infecting them with EBV in the laboratory). We will also put the special virus into these B cells so that they too have AdV/CMV. Again, these B cells will be treated with radiation so they cannot grow. Once we have made enough T cells we will test them to make sure they kill cells infected with Adenovirus and CMV. To make sure that these cells won't attack the patient's own healthy tissues, we test these cells against some of the blood cells that we will grow in the laboratory. These will be used to check to see if the AdV/CMV CTL can attack them. Alternatively, we may take blood from a first degree relative or take a small piece of skin from the patient to grow skin cells, which can also to be used to check if AdV/CMV CTL can attack them. The skin biopsy can be done at the same time as another procedure such as a bone marrow biopsy.

The cord donor's AdV/CMV CTL cells will be thawed and injected into the IV line over a period of up to 10 minutes.Patients may be premedicated with Benadryl and Tylenol. If the patient agrees and if he/she is well enough, one dose of CTL will be given on or after day 30 following transplant. If the patient does not have AdV/CMV infection we will not give antiviral medications to them during this study but we will monitor the patient closely to check for AdV/CMV infection. If the patient does have AdV/CMV infection before CTL infusion they may also be treated with antiviral medications during this study. We will monitor the patients closely for AdV/CMV infection by collecting blood and possibly urine and stool and testing them for AdV/CMV. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus Infection
• Communicable Diseases
• Cytomegalovirus Infection
• Cytomegalovirus Infections
• Infection

• NCT number: NCT00880789
• Study type: Interventional
• Source: Baylor College of Medicine
• Status: Completed
• Phase: Phase 1
• Start date: May 2009
• Completion date: June 2014