Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections
This trial is active, not recruiting.
|Treatments||cytomegalovirus ie-1-specific cytotoxic t lymphocytes, cytomegalovirus pp65-specific cytotoxic t lymphocytes, therapeutic allogeneic lymphocytes, polymerase chain reaction, flow cytometry, immunological diagnostic method, laboratory biomarker analysis|
|Sponsor||Milton S. Hershey Medical Center|
|Collaborator||National Cancer Institute (NCI)|
|Start date||August 2008|
|End date||August 2014|
|Trial size||20 participants|
|Trial identifier||NCT00769613, CDR0000615167, PSCI-PSHCI-08-051|
RATIONALE: White blood cells that have been treated in the laboratory may kill cells that are infected with cytomegalovirus.
PURPOSE: This phase I trial is studying how well cytotoxic T cells work in treating patients who have undergone donor stem cell transplant and have cytomegalovirus infections.
|Primary purpose||supportive care|
Time to development of cytomegalovirus (CMV)-specific immune reconstitution
CMV DNA levels
Time during post-infusion follow-up at which the dominant CMV pp65- and IE-1 epitopes for the donor is recognized by the cytotoxic T-cell lymphocytes (CTL)
Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors
Male or female participants at least 2 years old.
DISEASE CHARACTERISTICS: - Recipient of an allogeneic stem cell transplantation - Cytomegalovirus (CMV)-seropositive and meeting 1 of the following criteria: - Patient has a history of CMV antigenemia for ≥ 2 weeks - CMV DNA levels ≥ 600 copies/mcg of DNA despite antiviral therapy targeting CMV (e.g., ganciclovir or foscarnet) - No ongoing graft-vs-host disease - Has donor available for peripheral blood mononuclear cell collection (for cytotoxic T lymphocytes production), meeting either of the following criteria: - CMV-seropositive donor (≥ 2 years of age) - CMV-seronegative related donor (≥ 18 years of age) who consents to receive the CMV vaccine PATIENT CHARACTERISTICS: - ECOG performance status (PS) 0-3 OR Lansky PS 50-100% (for patients < 16 years of age) - Bilirubin < 2.0 mg/dL - AST and ALT < 2.5 times normal - Creatinine clearance ≥ 30 mL/min - Pulse oximetry ≥ 94% on no more than 40% oxygen by face mask - Not moribund - No patients expected to survive ≤ 1 month after the T-cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Must be on ≤ 1 mg/kg/day of prednisone or its equivalent at the time of study CTL infusion
|Official title||Emergency Access to C.V. pp65 / IE-1 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistant or Therapy Refractory Infections|
|Principal investigator||Kenneth G. Lucas, MD|
|Description||OBJECTIVES: Primary - To provide access to cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T lymphocytes (CTL) in patients with persistent CMV infections after allogeneic stem cell transplantation. Secondary - To characterize CMV pp65- and IE-1-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter. - To characterize the levels of CMV DNA in recipients of CMV pp65- and IE-1-specific CTL and observe whether the CTL infusion has any impact on level of virus. - To determine the feasibility of CMV CTL culture from CMV-seronegative donors who have received a CMV vaccine. OUTLINE: This is a multicenter study. Patients receive allogeneic cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T-cell lymphocytes infusion over 5 minutes on day 1. Patients may receive up to 2 more doses at least 2 weeks after previous dose. Blood samples are collected and analyzed by quantitative CMV PCR, chromium-release assays for CMV pp65- and IE-1-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45RA/RO. Intracellular cytofluorometry is used to assess IL-2, IL-4, IL-10, and IFN-γ production by CD4 and CD8 CMV-specific effector cells. After completion of study therapy, patients are followed periodically for up to 1 year.|
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