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To determine the safety of 2 intravenous injections of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with EBV-associated Hodgkin's Disease or lymphoma/lymphoproliferation/severe chronic EBV.
To determine the survival and the immune function of LMP-specific cytotoxic T-lymphocyte lines.
To assess the anti-viral and anti-tumor effects of LMP-specific CTLs.
To obtain preliminary information on the safety and response to an extended dosage regimen.
A total of 9 to 54 patients will be enrolled on study in one of 3 groups for each LMP-CTL product used. Group A is patients receiving CTLs as therapy for relapsed Lymphoma/lymphoepithelioma/leiomyosarcoma or EBV (associated)-T/NK-Lymphoproliferative Disorder or those patients who have a high risk of relapse. Group B is patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant and group C is patients receiving CTL as adjuvant therapy post allogeneic transplant. Three different dosing schedules will be evaluated. Three to six patients will be evaluated on each dosing schedule. Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules:
Group 1) Day 0: 2 x 10e7 cells/m2 and Day 14: 2 x 10e7 cells/m2
Group 2) Day 0: 2 x 10e7 cells/m2 and Day 14: 1 x 10e8 cells/m2
Group 3) Day 0: 1 x 10e8 cells/m2 and Day 14: 2 x 10e8 cells/m2
If patients with active disease have stable disease or a partial response by the RECIST criteria at their 8 week or subsequent evaluations they are eligible to receive up to 6 additional doses of CTLs at monthly intervals-each of which will consist of the same cell number as their second injection. Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion.
Patients will be premedicated with Benadryl 1mg/kg IV (max 50mg) and Tylenol 10mg/kg PO (max 650mg).
Cell Administration: LMP specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. Monitoring will be undertaken according to institutional standards for administration of blood products with the exception that the injection will be given by a physician.
Supportive Care: Patients will receive supportive care for acute or chronic toxicity, including blood components or antibiotics, and other intervention as appropriate. All treatments will be given at the Center for Cell and Gene Therapy, in Texas Childrens Hospital for children or The Methodist Hospital for adults.
PATIENT EVALUATION PRIOR TO ADMINISTRATION OF CTL:
1. Complete history and physical examination.
2. Other Studies The following investigations will be obtained pre-infusion, at 2, 4 and 6 weeks post-infusion and then at 3, 6, 9 and 12 months: CBC and differential, BUN, creatinine, bilirubin, SGOT, SGPT, alkaline phosphatase, Na, K, Cl, CO2, albumin, total protein
3. Diagnostic imaging to document measurable disease and response to therapy (CT scans, MRI, nuclear imaging) and/or blood tests (EBV viral load) to document measureable disease and response to therapy at pre-infusion and 6 weeks following the second infusion. If diagnostic imaging studies are performed at other times either during or after treatment on this study, that data will be collected and information gained will be used for this study. If the patient receives extended dosing, imaging will be done 1-3 months after the final infusion.
4. The following investigations will be obtained pre-infusion, 4 hours post infusion(optional depending on patient preference), at 3-4 days post infusion (optional depending on patient preference), 1, 2, 4 and 6 weeks post-infusion and then at 3, 6, 9, and 12 months and then yearly for 5 years. If the patient has additional injections of cells after the first two infusions, these tests will also be obtained pre each infusion, at the end of each infusion, 3-4 days post each infusion (optional depending on patient preference), and at 1, and 2 weeks post each infusion. Follow up will then continue 3 monthly and will continue until 12 months after the last infusion and then yearly for 5 years.
Peripheral blood in preservative free heparin and ACD (acid citrate dextrose) anticoagulant (20-40ml). This blood will be used for phenotyping of peripheral blood T cells and analysis of specificity of CTL response using HLA-peptide tetramer analysis and immune function assays including ELISPOT/ELISA and cytotoxicity assays. These studies will be done on patients on whom the appropriate reagents are available. Also PCR for EBV-DNA will be done to monitor the viral load.
If the patient has additional injections of cells after the first two infusions, these tests will also be obtained pre each infusion, at the end of each infusion, 3-4 days post each infusion (day optional depending on patient preference), and at 1, and 2 weeks post each infusion. Follow up will then continue 3 monthly and will continue until 12 months after the last infusion and then yearly thereafter for 2 years. No study specific blood tests will be done after two years (if the patients have had additional injections) but we will continue to keep in contact with patients to follow long term disease responses.
Other Tissues: Should the patient require a tumor biopsy at any stage during the first year, a sample of this will be used to assess EBV-DNA status.
If a patients hemoglobin is less than 8.0g/dl at any of the evaluation times, the amount of blood drawn for the evaluation will be reduced and may be obtained over more than one venipuncture, if necessary.
EVALUATION DURING STUDY
Patients shall be evaluated (seen in clinic or contacted by research coordinator) at two week intervals for the first eight weeks, then at 3, 6, 9 and 12 months, then yearly for 5 years. Additional visits will be obtained as clinically indicated or if the patient is having more than 2 infusions.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Injection of LMP Specific Cytotoxic T-Lymphocytes (group 1), Injection of LMP Specific Cytotoxic T-Lymphocytes (group 2), Injection of LMP Specific Cytotoxic T-Lymphocytes (group 3)
Texas Children's Hospital
Baylor College of Medicine
Published on BioPortfolio: 2014-08-27T03:55:08-0400
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