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

Sponsor

University Hospital Birmingham (Other)

Overall Status

Unknown status

CT.gov ID

NCT00986557

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Nonneoplastic Condition	Biological: adoptive immunotherapy Biological: alemtuzumab Biological: in vitro-treated peripheral blood lymphocyte therapy Drug: foscarnet sodium Drug: ganciclovir Genetic: polymerase chain reaction Procedure: allogeneic hematopoietic stem cell transplantation Procedure: infection prophylaxis and management Procedure: peripheral blood stem cell transplantation Procedure: standard follow-up care Radiation: radiation therapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

78 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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

Study Start Date :

Sep 1, 2009

Anticipated Primary Completion Date :

Aug 1, 2013

Outcome Measures

Primary Outcome Measures

CMV reactivation in the first year after ASCT measured by quantitative PCR []

Secondary Outcome Measures

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 []
Incidence of acute and chronic graft-versus-host disease []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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