Clinical trial NCT00002956: Immunotherapy for Lymphoproliferative Diseases Associated With Epstein-Barr Virus in Patients Who Have Undergone Organ Transplants
Official title: A Phase I Pilot Trial to Evaluate the Toxicity of Allogeneic Epstein-Barr Virus Specific T-Lymphocytes for the Treatment of EBV-Associated Lymphoproliferative Diseases in Organ Transplant Recipients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
recurrent childhood lymphoblastic lymphoma
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
T-cell large granular lymphocyte leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2004-07-19
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Donor lymphocytes that have been exposed to Epstein-Barr virus may be able to help the body kill cancers associated with this virus.

PURPOSE: Phase I trial to study the effectiveness of Epstein-Barr virus-specific T cells derived from matched donors in organ transplant patients with lymphoproliferative diseases associated with Epstein-Barr virus.

Detailed description: OBJECTIVES: I. Examine the toxic effects of allogeneic Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes (CTL) for the treatment of EBV lymphoproliferative diseases (LPD) in organ transplant recipients. II. Determine the level of in vivo expansion of allogeneic CTL and the period of time during which these CTL's can be detected in the blood of recipients of the T cell infusions.

OUTLINE: Donors undergo leukapheresis, and Epstein-Barr virus (EBV) specific cytoxic T lymphocytes are cultivated in vitro. Patients receive infusions of EBV specific cytotoxic T lymphocytes over 5 to 10 minutes on weeks 0, 2, and 4. Patients with stable disease and those achieving partial remission are followed weekly for signs of disease progression.

PROJECTED ACCRUAL: 10 patients will be accrued in this study.

Eligibility criteria: Inclusion criteria:

* Radiographic evidence of lymphadenopathy or lymphomatous lesions combined with clinical signs of Epstein-Barr virus lymphoproliferative disease (EBV LPD), such as fevers and lymphadenopathy
* following an organ transplant Persistent, progressive, or unresponsive disease despite decreased immunosuppression, chemotherapy, or radiation therapy EBV LPD must be of host origin
* At least 4 weeks
* Patients serologically hepatitis B and C positive may receive cytotoxic
* T- lymphocytes (CTL) from donors who are serologically positive for the same virus
* Must have an HLA identical or HLA haploidentical donor

Exclusion

* hepatic dysfunction SGOT/SGPT less than 2.5 times upper limit of normal (unless liver metastases present)
* Bilirubin less than 2.0 mg/dL
* renal dysfunction
* Creatinine clearance at greater than 50 mL/min
* cardiac dysfunction
* neurologic dysfunction
* pulmonary dysfunction
* patients developing EBV LPD who have a donor origin lymphoma
* HIV-1 positive
* Not capable of undergoing leukapheresis

Primary outcomes:
measure: Number of adverse events associated with administration of allogeneic Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes (CTL) for the treatment of EBV lymphoproliferative diseases (LPD) in organ transplant recipients
timeFrame: baseline to x weeks post infusion
measure: Mean length of time of allogeneic CTL during which these CTL's can be detected in the blood of recipients of the T cell infusions.
timeFrame: baseline to x weeks past infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Kenneth G. Lucas, MD
role: STUDY_CHAIR
References: