Vaccine Therapy in Treating Patients Who Have Undergone a Donor Stem Cell Transplant and Have Cytomegalovirus Infection That Has Not Responded to Therapy

Study Description

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Brief Summary:

RATIONALE: Vaccines may help the body build an effective immune response to kill cytomegalovirus infections.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients who have undergone a donor stem cell transplant and have cytomegalovirus infection that has not responded to therapy.

Condition or disease	Intervention/treatment	Phase
Cancer	Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes; Genetic: polymerase chain reaction; Other: diagnostic laboratory biomarker analysis; Other: flow cytometry; Other: immunologic technique	Phase 1

Detailed Description:

OBJECTIVES:

Primary

• To determine the safety of infusing cytomegalovirus (CMV) pp65-specific cytotoxic T-lymphocytes (CTL) generated using pp65 peptides in patients who have undergone allogeneic stem cell transplantation and have persistent CMV infections.

Secondary

• Characterize CMV pp65-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter.
• Characterize the levels of CMV DNA in recipients of CMV pp65 CTL and observe whether the CTL infusion has any impact on the level of virus.

OUTLINE: This is a multicenter study.

Patients receive cytomegalovirus (CMV) pp65 cytotoxic T-cell infusion 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-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45 RA/RD. 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 treatment, patients are followed periodically for up to 1 year.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Supportive Care
Official Title:	A Phase I Trial to Examine the Safety, Clinical, Immunologic and Virologic Effects of CMV pp65 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistent or Therapy Refractory Infections
Study Start Date :	June 2007
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	December 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Single arm study	Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes Genetic: polymerase chain reaction Other: diagnostic laboratory biomarker analysis Other: flow cytometry Other: immunologic technique

Outcome Measures

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Primary Outcome Measures :

1. Toxicity [ Time Frame: 1 year ]
2. Treatment failure [ Time Frame: 1 year ]
3. Safety [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Time to development of cytomegalovirus (CMV) specific immune reconstitution [ Time Frame: 1 year ]
2. CMV DNA levels [ Time Frame: 1 year ]
3. Time during post-infusion follow up at which the dominant CMV pp65 epitope for the donor is recognized by the cytotoxic t-cell lymphocyte recipient [ Time Frame: 1 year ]

Eligibility Criteria

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Ages Eligible for Study:	2 Years to 120 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Cytomegalovirus (CMV) seropositive

  • Patient has had CMV antigenemia for ≥ 2 weeks OR CMV DNA levels ≥ 600 copies/μg of DNA despite antiviral therapy targeting CMV (ganciclovir or foscarnet)
• No prior allogeneic stem cell transplantation before the most recent transplantation
• CMV seropositive donor negative for HIV-1, HIV-2, HTLV-1/2 available

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2 (for patients ≤ 16 years of age) OR Lansky performance status 70-100%
• Bilirubin < 2.0 mg/dL
• AST and ALT < 2.5 times upper limit of normal
• Creatinine clearance > 50 mL/min
• Pulse oximetry > 95% without supplemental oxygen
• No history of graft-vs-host disease (GVHD) ≥ grade 2
• Not moribund
• No patients not expected to survive 1 month after T cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction

PRIOR CONCURRENT THERAPY:

• No concurrent systemic immunosuppressive agents for the treatment of GVHD

Contacts and Locations

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Locations

United States, Pennsylvania
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850

Sponsors and Collaborators

University of Louisville

Penn State University

Investigators

Principal Investigator:	Kenneth G. Lucas, MD	Milton S. Hershey Medical Center

More Information

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Responsible Party:	University of Louisville
ClinicalTrials.gov Identifier:	NCT00509691 History of Changes
Other Study ID Numbers:	CDR0000557037; PSCI-25114
First Posted:	July 31, 2007
Last Update Posted:	May 9, 2017
Last Verified:	May 2017

Keywords provided by University of Louisville:

infection; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; atypical chronic myeloid leukemia, BCR-ABL1 negative; blastic phase chronic myelogenous leukemia; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; chronic eosinophilic leukemia

primary myelofibrosis; chronic myelomonocytic leukemia; chronic neutrophilic leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; disseminated neuroblastoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; juvenile myelomonocytic leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; nodal marginal zone B-cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:

Infection; Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases