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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Graft Versus Host Disease, Nonneoplastic Condition

Intervention / Treatment
-----------------
* 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


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: adoptive immunotherapy|nan|
|Biological: alemtuzumab|nan|
|Biological: in vitro-treated peripheral blood lymphocyte therapy|nan|
|Drug: foscarnet sodium|nan|
|Drug: ganciclovir|nan|
|Genetic: polymerase chain reaction|nan|
|Procedure: allogeneic hematopoietic stem cell transplantation|nan|
|Procedure: infection prophylaxis and management|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Procedure: standard follow-up care|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMV reactivation in the first year after ASCT measured by quantitative PCR |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cytomegalovirus infection, graft versus host disease