T-Lymphocyte Infusion or Standard Therapy in Treating Patients at Risk of Cytomegalovirus Infection After a Donor Stem Cell Transplant

A Randomised Controlled Phase II Trial of the Adoptive Transfer of Selected Cytomegalovirus-Specific Cytotoxic T Lymphocytes (CMV-CTL) After Allogeneic Stem Cell Transplantation (SCT) in Patients at Risk of CMV Disease

RATIONALE: An infusion of cytomegalovirus-specific T lymphocytes may prevent or reduce cytomegalovirus infection during the first year after a donor stem cell transplant.

PURPOSE: This randomized phase II trial is studying T-lymphocyte infusion to see how well it works compared with standard therapy in treating patients at risk of cytomegalovirus infection after a donor stem cell transplant.

Study Overview

• Status: Unknown
• Conditions: Graft Versus Host Disease; Nonneoplastic Condition
• Intervention / Treatment: Radiation: radiation therapy; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Biological: alemtuzumab; Genetic: polymerase chain reaction; Procedure: standard follow-up care; Drug: ganciclovir; Biological: adoptive immunotherapy; Biological: in vitro-treated peripheral blood lymphocyte therapy; Drug: foscarnet sodium; Procedure: infection prophylaxis and management

Detailed Description

OBJECTIVES:

Primary

• To determine the frequency of cytomegalovirus (CMV) reactivation during the first year after allogeneic stem cell transplantation (ASCT) in patients at risk for CMV infection treated with adoptive transfer of selected CMV-specific cytotoxic T-lymphocytes.

Secondary

• To monitor CMV-specific immune reconstitution within the first year following ASCT in these patients.
• To determine the time to CMV reactivation in these patients.
• To evaluate the use of antiviral therapy in these patients.
• To determine the incidence of secondary CMV reactivation and CMV disease in patients treated with this regimen.
• To determine the incidence of acute and chronic graft-versus-host disease.

OUTLINE: This is a multicenter study. After undergoing an allogeneic peripheral blood stem cell transplantation (PBSCT) using an alemtuzumab-based conditioning regimen that also includes radiotherapy, patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cytomegalovirus (CMV)-specific cytotoxic T-lymphocyte infusion on day 21-90 after allogeneic PBSCT.
• Arm II: Patients undergo standard follow-up care and receive standard antiviral therapy comprising ganciclovir IV or foscarnet sodium upon detection or confirmation of CMV reactivation.

Blood samples are collected to assess CMV viral load by quantitative PCR.

After completion of study therapy, patients are followed once a week for 100 days and then once a month for 1 year.

PROJECTED ACCRUAL: A total of 18 patients with sibling donors and 21 patients with unrelated donors are accrued for each arm, resulting in a total of 78 patients accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2SG
      • Recruiting
      • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
      • Contact: Frederick Chen, MD; Phone Number: 44-121-253-4174

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Planning allogeneic peripheral blood stem cell transplantation (PBSCT) using a conditioning regimen containing alemtuzumab and radiotherapy

• Sibling or matched unrelated donor available

  • Patients and donor matched for ≥ one of the following HLA alleles:

    • HLA-A*0101
    • HLA*0201
    • HLA-A*1101
    • HLA-A*2402
    • HLA-B*0702
    • HLA-B*0801
    • HLA-B*3502
  • No donors whose stem cells have already been collected and cryopreserved prior to transplant
• Patient and donor must be CMV seropositive
• Stem cell harvests ≥ 4.0 x 10^6 CD34 cells/kg

PATIENT CHARACTERISTICS:

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior bone marrow transplantation
• No concurrent participation in another therapeutic transplantation study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
CMV reactivation in the first year after ASCT measured by quantitative PCR

Secondary Outcome Measures

Outcome Measure
Incidence of acute and chronic graft-versus-host disease
CMV-specific T-cell reconstitution by detection of circulating T-cell responses to CMV in the first year after ASCT
Time to CMV reactivation
Use of antiviral therapy
Incidence of secondary CMV reactivation and CMV disease

Collaborators and Investigators

• Sponsor: University Hospital Birmingham
• Investigators: Principal Investigator: Frederick Chen, MD, University Hospital Birmingham

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ANTICIPATED): August 1, 2013

Study Registration Dates

• First Submitted: September 29, 2009
• First Submitted That Met QC Criteria: September 29, 2009
• First Posted (ESTIMATE): September 30, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: cytomegalovirus infection; graft versus host disease
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Immune System Diseases; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Alemtuzumab; Ganciclovir; Ganciclovir triphosphate; Foscarnet; Phosphonoacetic Acid
• Other Study ID Numbers: CDR0000650654; CRC-TU-ACE-CMV; 53325562; EU-20974