Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder
Condition: EBV-Related Post-Transplant Lymphoproliferative Disorder; Monomorphic Post-Transplant Lymphoproliferative Disorder; Polymorphic Post-Transplant Lymphoproliferative Disorder; Recurrent Monomorphic Post-Transplant Lymphoproliferative Disorder; Recurrent Polymorphic Post-Transplant Lymphoproliferative Disorder; Refractory Monomorphic Post-Transplant Lymphoproliferative Disorder; Refractory Polymorphic Post-Transplant Lymphoproliferative Disorder
MeSH terms: Lymphoproliferative Disorders; Recurrence
Intervention: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes; Rituximab
Intervention description: Given IV; Given IV
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Maximum age: 29 Years
Healthy volunteers: No

Summary:

      This pilot phase II trial studies how well 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. Rituximab is a monoclonal antibody that may interfere with the
      ability of cancer cells to grow and spread. LMP-specific T-cells are special immune system
      cells trained to recognize proteins found on post-transplant lymphoproliferative disorder
      tumor cells if they are infected with Epstein-Barr virus. Giving rituximab and LMP-specific
      T-cells may work better in treating pediatric organ recipients with post-transplant
      lymphoproliferative disorder than rituximab alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have a history of solid organ transplantation

          -  Patients must have biopsy-proven newly diagnosed, relapsed or refractory 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 evaluable disease at study entry either by imaging or by serial
             endoscopic biopsies.

               -  Note: a measurable node must have an LDi (longest diameter) greater than 1.5 cm;
                  a measurable extranodal lesion should have an LDi greater than 1.0 cm; all tumor
                  measurements must be recorded in millimeters (or decimal fractions of
                  centimeters)

          -  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

               -  Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years
                  of age

          -  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

          -  Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto
             this study

          -  COHORT A and B: Patient must not have received therapy with anti-CD20 monoclonal
             antibodies within 90 days of entry onto this study

          -  COHORT C: Patient must have received rituximab at 375 mg/m^2 weekly for at least 3
             doses within the last 90 days prior to study enrollment

          -  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

          -  COHORT C: HLA typing is available and will be submitted at the time of enrollment.

        Exclusion Criteria:

          -  Burkitt morphology

          -  Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar
             puncture

               -  Note: lumbar puncture can be performed at the time of diagnosis and does not need
                  to be repeated unless there is a change in neurological status or it was
                  performed more than 14 days prior to study entry

          -  Bone marrow involvement (> 25%)

               -  Note: bone marrow aspiration/biopsy can be performed at the time of diagnosis and
                  does not need to be repeated unless there is a change in peripheral blood counts
                  or it was performed more than 14 days prior to study entry

          -  Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence
             of multi-organ involvement/failure including two or more of the following:

               -  Bone marrow (including pancytopenia without any detectable B-cell proliferation)

               -  Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)

               -  Lungs (interstitial pneumonitis with or without pleural effusions)

               -  Gastrointestinal hemorrhage

          -  Any documented donor-derived PTLD

          -  Hepatitis B or C serologies 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 since there is no available information regarding
             human fetal or teratogenic toxicities

          -  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 and for 12 months following completion of study therapy.

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met