Donor Cytotoxic T-Lymphocytes in Treating Patients With Relapsed Epstein-Barr Virus-Associated Diseases
The purpose of this study is to obtain some of the donor's blood to make latent membrane protein (LMP)-specific cytotoxic T-lymphocytes (CTLs) so they would be available to potentially treat a recipient who had cancer of other disease associated with Epstein-Barr virus (EBV).
Inclusion Criteria
- SCREENING
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: * Hodgkin lymphoma * Non-Hodgkin lymphoma * Lymphoproliferative disorder * Nasopharyngeal carcinoma * Leiomyosarcoma * Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or peripheral blood mononuclear cell (PBMC) (> 4000 genomes per ug PBMC deoxyribonucleic acid [DNA]) and/or biopsy tissue positive for EBV
- Karnofsky/Lansky score >= 50%
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy
- TREATMENT
- Any patients, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: * Hodgkin lymphoma * Non-Hodgkin lymphoma * Lymphoproliferative disorder * Nasopharyngeal carcinoma * Leiomyosarcoma * Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (> 4000 genomes per Mg PBMC DNA) and/or biopsy tissue positive EBV
- The disease needs to be in one of the following stages: * At diagnosis or in first relapse AND the patient is unable to receive conventional chemotherapy for his/her condition * In second or subsequent relapse * With residual disease after autologous, syngeneic or allogeneic hematopoietic stem cell transplantation (HSCT)
- Life expectancy >= 6 weeks
- Tumor tissue is positive for EBV
- Karnofsky/Lansky score >= 50%
- Bilirubin < 3 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) < 5 x ULN
- Hemoglobin (Hgb) > 8.0 g/dL
- Serum creatinine < 3 x ULN
- Pulse oximetry of > 90% on room air
- If post allogeneic HSCT, patient must not have less than 50% donor chimerism in either peripheral blood or bone marrow
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone at time of treatment
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded; the male partner should use condom
Exclusion Criteria
- SCREENING
- Know human immunodeficiency virus (HIV) positivity
- TREATMENT
- Currently receiving any investigational agents or have received any tumor vaccines within previous 4 weeks
- Active acute grade III-IV graft-versus-host disease
- Severe intercurrent infection
- Received alemtuzumab or other anti-Tcell antibody within 28 days
- HIV seropositivity
- Pregnancy (due to unknown effects of this therapy on a fetus) or lactation
- Tumor in a location where enlargement could cause airway obstruction
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01447056.
PRIMARY OBJECTIVES:
I. To determine the safety of intravenous injections of third-party, partially human leukocyte antigen (HLA)-matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma).
SECONDARY OBJECTIVES:
I. To determine the survival and the immune function of third-party allogeneic EBV-specific CTL lines.
II. To assess anti-EBV and anti-tumor effects of third-party partially HLA-matched allogeneic EBV-specific CTL lines.
III. To obtain preliminary information on the safety and response to a repeated dosage regimen.
OUTLINE: This is a dose-escalation study.
Patients receive allogeneic LMP1-/LMP2- specific CTL intravenously (IV) over 1-10 minutes on day 0. Patients achieving partial response or stable disease may receive up to 5 additional infusions every 4-6 weeks at the discretion of attending physician.
After completion of study treatment, patients are followed up every 3 months for 1 year and then yearly for 5 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorCarlos Almeida Ramos
- Primary IDMALTED
- Secondary IDsNCI-2012-01079, H-28361
- ClinicalTrials.gov IDNCT01447056