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

Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00986557
• Other study ID #: CDR0000650654
• Secondary ID: CRC-TU-ACE-CMV53
• Status: Recruiting
• Phase: Phase 2
• First received: September 29, 2009
• Last updated: August 23, 2013
• Start date: September 2009

Study information

• Verified date: April 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Graft Versus Host Disease
• Graft vs Host Disease
• Nonneoplastic Condition

Intervention

Biological:
• adoptive immunotherapy

• alemtuzumab

• in vitro-treated peripheral blood lymphocyte therapy

Drug:
• foscarnet sodium

• ganciclovir

Genetic:
• polymerase chain reaction

Procedure:
• allogeneic hematopoietic stem cell transplantation

• infection prophylaxis and management

• peripheral blood stem cell transplantation

• standard follow-up care

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMV reactivation in the first year after ASCT measured by quantitative PCR			No
Secondary	CMV-specific T-cell reconstitution by detection of circulating T-cell responses to CMV in the first year after ASCT			No
Secondary	Time to CMV reactivation			No
Secondary	Use of antiviral therapy			No
Secondary	Incidence of secondary CMV reactivation and CMV disease			No
Secondary	Incidence of acute and chronic graft-versus-host disease			No