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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Cancer

Intervention / Treatment
-----------------
* Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes
* Genetic: polymerase chain reaction
* Other: diagnostic laboratory biomarker analysis
* Other: flow cytometry
* Other: immunologic technique


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm study<br> | Biological: cytomegalovirus pp65-specific cytotoxic T lymphocytes<br> <br> Genetic: polymerase chain reaction<br> <br> Other: diagnostic laboratory biomarker analysis<br> <br> Other: flow cytometry<br> <br> Other: immunologic technique<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 1 year | 
| Treatment failure |  | 1 year | 
| Safety |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to development of cytomegalovirus (CMV) specific immune reconstitution |  | 1 year | 
| CMV DNA levels |  | 1 year | 
| 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 |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, high risk metastatic gestational trophoblastic tumor, previously treated childhood rhabdomyosarcoma, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent breast cancer, recurrent/refractory childhood Hodgkin lymphoma, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood rhabdomyosarcoma, recurrent childhood small noncleaved cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent neuroblastoma, recurrent ovarian epithelial cancer, recurrent ovarian germ cell tumor, recurrent small lymphocytic lymphoma, recurrent malignant testicular germ cell tumor, recurrent Wilms tumor and other childhood kidney tumors, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, refractory multiple myeloma, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, splenic marginal zone lymphoma, stage I multiple myeloma, stage II multiple myeloma, stage III adult Burkitt lymphoma, stage III adult Hodgkin lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III chronic lymphocytic leukemia, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III multiple myeloma, stage III small lymphocytic lymphoma, stage III malignant testicular germ cell tumor, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV adult Burkitt lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV breast cancer, stage IV chronic lymphocytic leukemia, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV ovarian epithelial cancer, stage IV small lymphocytic lymphoma, stage IIA ovarian epithelial cancer, stage IIA ovarian germ cell tumor, stage IIB ovarian epithelial cancer, stage IIB ovarian germ cell tumor, stage IIC ovarian epithelial cancer, stage IIC ovarian germ cell tumor, stage IIIA ovarian epithelial cancer, stage IIIA ovarian germ cell tumor, stage IIIB ovarian epithelial cancer, stage IIIB ovarian germ cell tumor, stage IIIC ovarian epithelial cancer, stage IIIC ovarian germ cell tumor, stage IV ovarian germ cell tumor