Clinical trial NCT00509691: Vaccine Therapy in Treating Patients Who Have Undergone a Donor Stem Cell Transplant and Have Cytomegalovirus Infection That Has Not Responded to Therapy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: 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
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: Penn State University
First posted: 2007-07-31
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Toxicity
timeFrame: 1 year
measure: Treatment failure
timeFrame: 1 year
measure: Safety
timeFrame: 1 year
Secondary outcomes:
measure: Time to development of cytomegalovirus (CMV) specific immune reconstitution
timeFrame: 1 year
measure: CMV DNA levels
timeFrame: 1 year
measure: 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
timeFrame: 1 year
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Kenneth G. Lucas, MD
role: PRINCIPAL_INVESTIGATOR
References: