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

University Hospitals Birmingham NHS Foundation Trust (UHB)

Status and phase: Unknown; Phase 2

Conditions: Graft Versus Host Disease; Nonneoplastic Condition

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00986557

53325562

CDR0000650654

CRC-TU-ACE-CMV

EU-20974

Details and patient eligibility

About

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.

Full 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.

Enrollment: 78 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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