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

NCT00078533 | Completed Phase 1 DMC

• 3 other identifiers: 12683-VICTAVICTAPACT 001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

Patients 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. We are asking patients to participate in this study which tests if blood cells from the donor that have been grown in a special way, can prevent the 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 patient and/or their donor is positive for CMV, they are at risk of developing CMV disease while the patients 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, Foscarnet, or Cidofovir . 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, the 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 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 patients 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). Doctors at other places have used similar T cells to treat or prevent CMV infections after transplant and have not seen any significant problems. These CMV specific cytotoxic T cells are an investigational product not approved by the Food and Drug Administration.

Conditions

Cytomegalovirus Infections

Keywords

Allogeneic; Transplant; CMV; Stem Cell; Donor; Allogeneic stem cell recipients at risk for CMV reactivation

Outcome Measures

Primary Outcomes (2)

• safety, toxicity and maximum tolerated dose (MTD)

  30 days

• Efficacy of recovery of virus-specific immunity and correlation with protection from viral reactivation/disease.

  8 weeks

Study Arms (1)

CMV CTL infusion

EXPERIMENTAL

Subjects are assigned a dose level at the time of enrollment.

Biological: CMV CTL infusion

Interventions

CMV CTL infusion BIOLOGICAL

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

CMV CTL infusion

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 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 or other antiviral therapy for CMV reactivation
• Patient/guardian able to give informed consent

You may not qualify if:

• 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

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 (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Keller MD, Darko S, Lang H, Ransier A, Lazarski CA, Wang Y, Hanley PJ, Davila BJ, Heimall JR, Ambinder RF, Barrett AJ, Rooney CM, Heslop HE, Douek DC, Bollard CM. T-cell receptor sequencing demonstrates persistence of virus-specific T cells after antiviral immunotherapy. Br J Haematol. 2019 Oct;187(2):206-218. doi: 10.1111/bjh.16053. Epub 2019 Jun 20.

  PMID: 31219185 DERIVED

• Hanley PJ, Cruz CR, Savoldo B, Leen AM, Stanojevic M, Khalil M, Decker W, Molldrem JJ, Liu H, Gee AP, Rooney CM, Heslop HE, Dotti G, Brenner MK, Shpall EJ, Bollard CM. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood. 2009 Aug 27;114(9):1958-67. doi: 10.1182/blood-2009-03-213256. Epub 2009 May 14.

  PMID: 19443656 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Helen E Heslop, 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: Professor of Medicine and Pediatrics

Study Record Dates

• First Submitted: March 1, 2004
• First Posted: March 2, 2004
• Study Start: April 1, 2004
• Primary Completion: July 1, 2010
• Study Completion: June 1, 2011
• Last Updated: October 8, 2014

Record last verified: 2014-06

Locations

US (2)