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
2 Years
N/A
Both
Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Toxicity
Outcome Time Frame:
1 year
Safety Issue:
Yes
Principal Investigator
Kenneth G. Lucas, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Milton S. Hershey Medical Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000557037
NCT ID:
NCT00509691
Start Date:
June 2007
Completion Date:
December 2011
Related Keywords:
- Cancer
- 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
- Cytomegalovirus Infections
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
