Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections

NCT ID: NCT00769613

Last Updated: 2013-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cancer

Keywords

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stage III adult Burkitt 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 Hodgkin lymphoma stage III adult immunoblastic large cell lymphoma stage III adult lymphoblastic lymphoma 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 small lymphocytic lymphoma stage IV adult Burkitt 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 Hodgkin lymphoma stage IV adult immunoblastic large cell lymphoma stage IV adult lymphoblastic lymphoma 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 small lymphocytic lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult Hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma 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 small lymphocytic lymphoma recurrent/refractory childhood Hodgkin lymphoma recurrent mycosis fungoides/Sezary syndrome extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone 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 accelerated phase chronic myelogenous leukemia adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission 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) 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 myelomonocytic leukemia chronic phase chronic myelogenous leukemia juvenile myelomonocytic leukemia recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia refractory chronic lymphocytic leukemia refractory hairy cell leukemia relapsing chronic myelogenous leukemia secondary acute myeloid leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia childhood myelodysplastic syndromes chronic eosinophilic leukemia primary myelofibrosis chronic neutrophilic leukemia de novo myelodysplastic syndromes disseminated neuroblastoma myelodysplastic/myeloproliferative neoplasm, unclassifiable high risk metastatic gestational trophoblastic tumor previously treated childhood rhabdomyosarcoma previously treated myelodysplastic syndromes recurrent Wilms tumor and other childhood kidney tumors recurrent childhood rhabdomyosarcoma recurrent neuroblastoma recurrent ovarian epithelial cancer recurrent ovarian germ cell tumor recurrent malignant testicular germ cell tumor secondary myelodysplastic syndromes stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma stage II ovarian epithelial cancer stage III ovarian epithelial cancer stage IV ovarian epithelial cancer stage III malignant testicular germ cell tumor stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer refractory multiple myeloma cytomegalovirus infection

Study Design

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Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Interventions

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cytomegalovirus IE-1-specific cytotoxic T lymphocytes

Intervention Type BIOLOGICAL

cytomegalovirus pp65-specific cytotoxic T lymphocytes

Intervention Type BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

polymerase chain reaction

Intervention Type GENETIC

flow cytometry

Intervention Type OTHER

immunological diagnostic method

Intervention Type OTHER

laboratory biomarker analysis

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role lead

Principal Investigators

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Kenneth G. Lucas, MD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Locations

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Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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PSCI-PSHCI-08-051

Identifier Type: -

Identifier Source: secondary_id

CDR0000615167

Identifier Type: -

Identifier Source: org_study_id