A Pilot Study of Rituximab (RTX) and Third Party Latent Membrane Protein (LMP)-Specific Cytotoxic T-Lymphocytes in Pediatric Solid Organ Recipients (SOT) With EBV-Positive CD20-Positive Post-Transplant Lymphoproliferative Disease (PTLD)
Exploring the Use of T-Cell Therapy in Treating Epstein-Barr Virus Positive Post-Transplant Disorder
Brief description of study.
This pilot clinical trial studies how rituximab and latent membrane protein (LMP)-specific T-cells work in treating pediatric solid organ recipients with Epstein-Barr virus-positive, cluster of differentiation (CD)20-positive post-transplant lymphoproliferative disorder.
Detailed description of study
The purpose of this study is to determine the feasibility of treating pediatric and young adult solid organ transplant recipients with newly diagnosed or recurrent Epstein-Barr virus (EBV)-positive CD20-positive post-transplant lymphoproliferative disease (PTLD) with a novel T cell therapeutic, allogeneic Latent Membrane Protein(LMP)1/LMP2-specific cytotoxic T-lymphocytes (third party latent membrane protein [LMP]-specific T cells), in a cooperative group setting.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Lymphoproliferative Disorder
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Age: 29 years or below
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Gender: All
Inclusion Criteria
Patient must have a history of solid organ transplantation
Patients must have biopsy-proven newly diagnosed polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is - CD20 positive
EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ hybridization (preferred) and/or LMP immunoperoxidase staining
There must be measurable disease at study entry (the presence of at least one lesion that can be accurately measured in at least one dimension with the longest diameter at least 10 mm using computer tomography scanning)
Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1
Patients must have a life expectancy of >= 8 weeks
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Must not have received myelosuppressive chemotherapy within 2 weeks of entry onto this study
Must not have received therapy with anti-CD20 monoclonal antibodies within 90 days of entry onto this study
Must not have received any prior radiation to any sites of measurable disease
Must not have received any prior stem cell transplant
Must not have received investigational therapy within 30 days of entry onto this study - Must not have received prior EBV or LMP-specific T cells within 90 days of entry onto this study
Must not have received alemtuzumab or other anti-T-cell antibody therapy within 28 days of entry onto this study
Exclusion Criteria
Burkitt morphology
Any documented donor-derived PTLD
Central nervous system (CNS) involvement
Bone marrow involvement
Hepatitis B and C serologies that are consistent with past or current infections because of the risk of reactivation with rituximab
Severe and/or symptomatic refractory concurrent infection other than EBV
Pregnant females are ineligible
Lactating females are not eligible unless they have agreed not to breastfeed their infants
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
This study investigates the use of a special type of immune cell treatment, called T-cell therapy, in children and young adults who have had an organ transplant and developed a condition known as post-transplant lymphoproliferative disorder (PTLD). PTLD is a complication that can happen after an organ transplant, where cells in the body grow out of control. The study focuses on a type of PTLD that is positive for Epstein-Barr virus (EBV) and a protein called CD20.
Participants in the study will receive a treatment involving T-cells that are specifically designed to target and fight the EBV virus. These T-cells are known as LMP-specific T-cells, which are engineered to recognize and attack cells expressing latent membrane proteins associated with the virus. The study will examine how these T-cells work in treating the disorder, and whether this approach is feasible for patients.
- Who can participate: Participants must have had a solid organ transplant, developed a specific type of PTLD that is CD20 and EBV positive, and have measurable disease. They must be medically unable to reduce immunosuppression without risk and must not have certain prior treatments or conditions like central nervous system involvement or hepatitis infections.
- Study details: Participants will receive T-cell therapy, using specially prepared cells to target the virus. Some participants may receive a placebo, an inactive substance that looks like the investigational medicine but does not contain any medicine.
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