Graft Versus Host Disease, Nonneoplastic Condition
Conditions
Keywords
cytomegalovirus infection, graft versus host disease
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.
Interventions
BIOLOGICALadoptive immunotherapy
BIOLOGICALalemtuzumab
BIOLOGICALin vitro-treated peripheral blood lymphocyte therapy
DRUGfoscarnet sodium
DRUGganciclovir
GENETICpolymerase chain reaction
PROCEDUREallogeneic hematopoietic stem cell transplantation
PROCEDUREinfection prophylaxis and management
PROCEDUREperipheral blood stem cell transplantation
PROCEDUREstandard follow-up care
RADIATIONradiation therapy
Sponsors
University Hospital Birmingham
Study design
Allocation
RANDOMIZED
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CMV reactivation in the first year after ASCT measured by quantitative PCR | — |
Secondary
| Measure | 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 | — |
Countries
United Kingdom
Outcome results
None listed