Clinical trial NCT00986557: T-Lymphocyte Infusion or Standard Therapy in Treating Patients at Risk of Cytomegalovirus Infection After a Donor Stem Cell Transplant
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Graft Versus Host Disease
Nonneoplastic Condition
Keywords: cytomegalovirus infection
graft versus host disease
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-09-30
Enrollment: 78
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: CMV reactivation in the first year after ASCT measured by quantitative PCR
Secondary outcomes:
measure: CMV-specific T-cell reconstitution by detection of circulating T-cell responses to CMV in the first year after ASCT
measure: Time to CMV reactivation
measure: Use of antiviral therapy
measure: Incidence of secondary CMV reactivation and CMV disease
measure: Incidence of acute and chronic graft-versus-host disease
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
Study officials:
affiliation: University Hospital Birmingham
name: Frederick Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: