Cytotoxic T-Lymphocytes for the Prophylaxis of Cytomegalovirus After Allogeneic Stem Cell Transplant - Full Text View

Purpose

Patients enrolled on this study have a type of blood cell cancer, other blood disease or a genetic disease for which they will receive a stem cell transplant. The donor of the stem cells will be either a brother or sister or another relative or a closely matched unrelated donor. This study tests if blood cells from the donor, that have been grown in a special way, can prevent patients from getting an infection with a virus called Cytomegalovirus or CMV.

CMV is a virus that can cause serious infections in patients with suppressed immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, the liver and the eyes. Approximately 2/3 of normal people harbor this virus in their body. In healthy people CMV rarely causes any problems because the immune system can keep it under control. If the donor is positive for CMV, patients are at risk of developing CMV disease while their immune system is weak post transplant. Usually, this risk is highest during the first 3-4 months after the transplant.

CMV disease can be prevented during this time in most people by using drugs that can kill the virus such as Ganciclovir or Foscarnet. However, these medications have many side effects and have to be given daily by vein for approximately 4-5 months after transplant. One of the side effects is that it takes the new immune system much longer to develop an effective defense against the virus. Therefore, once the medicines are stopped, patients still have a chance to develop CMV disease.

We want to see if we can use a kind of white blood cell called T cells that we have grown from the patients stem cell donor instead of the regular treatment with Ganciclovir or Foscarnet to prevent CMV from "flaring up". These cells have been trained to attack CMV virus infected cells. We will grow these T cells from blood taken from the donor before the transplant. These cells are called CMV-specific cytotoxic T-lymphocytes or CMV CTL and they will be given to the patient around 30 days after their transplant.

We have used this sort of therapy to treat a different virus which can cause problems after transplant called Epstein Barr Virus (EBV).

Condition	Intervention	Phase
Stem Cell Transplantation Cytomegalovirus Infections	Biological: CMV CTL infusion	Phase I Phase II

MedlinePlus related topics:

Cytomegalovirus Infections

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title:	Virus Specific Cytotoxic T-Lymphocytes for the Treatment of CMV After Allogeneic Stem Cell Transplant: A Dose-Finding Trial

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

safety, toxicity and maximum tolerated dose (MTD) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
Efficacy of recovery of virus-specific immunity and correlation with protection from viral reactivation/disease. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2004
Estimated Study Completion Date:	December 2021
Estimated Primary Completion Date:	December 2021 (Final data collection date for primary outcome measure)

Intervention Details:

Three dose levels will be explored. The lowest dose level will be 1x10^7cells/m2 and the highest will be 1x10^8/m2. 3-6 pts will be entered at each dose level (depending on toxicity). If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval. Additional patients will be treated at dose level 1 in order to assess the secondary objective of virus-specific immunity from the CTL infusions

Detailed Description:

Patients will be evaluated in the clinic and will be eligible to receive CTL from day 30 post transplant if they meet eligibility criteria. CMV specific T cells will be thawed and given by intravenous injection. This is a traditional Phase I dose escalation study of one infusion of CMV-specific CTL given to patients at risk for CMV reactivation after matched related or mismatched related donor stem cell transplant. Three dose levels will be explored. The lowest dose level will be 1x10e7cells/m2 and the highest will be 1x10e8/m2. Three to six patients will be entered at each dose level (depending on toxicity) following the scheme below. This approach was successfully used in optimizing our EBV CTL infusion regime. If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Recipients of allogeneic donor stem cell transplants at risk for CMV reactivation with a CMV seropositive stem cell donor and at least 30 days post transplant.
Recipients can have early evidence of CMV reactivation with greater than 2 leukocytes but less than 10 leukocytes positive for the CMV Ag per 100,000 cells.
No evidence of graft-versus-host disease (GVHD) > Grade II at time of enrollment.
Life expectancy > 30 days
No severe intercurrent infections
Lansky/Karnofsky scores greater than or equal to 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)
Not receiving Ganciclovir, Foscarnet, or Cidofovir
Patient/guardian able to give informed consent

Exclusion Criteria:

Patients with CMV negative stem cell donors
Patients with GVHD Grades III-IV
Patients receiving antiviral therapy for CMV reactivation or other viral infections such as adenovirus or herpes viruses
Patients with significant CMV reactivation. Significant CMV reactivation is defined as one CMV Antigenemia reading with >10 leukocytes positive for the CMV Ag per 100,000 cells
Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078533

Locations


United States, Texas
	The Methodist Hospital	Recruiting
	Houston, Texas, United States, 77030
	Contact: CATHERINE M BOLLARD, MD 832-824-4781 cmbollar@texaschildrenshopsital.org
	Texas Children's Hospital	Recruiting
	Houston, Texas, United States, 77030
	Contact: Catherine M Bollard, MD 832-824-4781 cmbollar@texaschildrenshopsital.org

Sponsors and Collaborators

Baylor College of Medicine

The Methodist Hospital System

Texas Children's Hospital

Center for Cell and Gene Therapy

Investigators


Study Chair:	Malcolm K Brenner, MD	Baylor College of Medicine

More Information

Responsible Party:	Baylor College of Medicine ( Helen Heslop )
Study ID Numbers:	H12683, VICTA
First Received:	March 1, 2004
Last Updated:	May 7, 2008
ClinicalTrials.gov Identifier:	NCT00078533
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

Allogeneic

Transplant

CMV

Stem Cell

Donor

Allogeneic stem cell recipients at risk for CMV reactivation

Study placed in the following topic categories:

Virus Diseases

Signs and Symptoms

Cytomegalovirus Infections

DNA Virus Infections

Cytomegalic inclusion disease

Cytomegalovirus

Herpesviridae Infections

Additional relevant MeSH terms:

Infection

ClinicalTrials.gov processed this record on November 20, 2008

Sponsors and Collaborators:	Baylor College of Medicine The Methodist Hospital System Texas Children's Hospital Center for Cell and Gene Therapy
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00078533