Phase 2
N=18
Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder
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
Bottom Line
View on ClinicalTrials.gov: NCT02900976 ↗Enrolled (actual)
18
Serious AEs
20.0%
Results posted
Jun 2022
Primary outcome: Primary: Percentage of Patients Assigned to Arm Latent Membrane Protein-specific T-cells (LMP-TC) With Successful LMP-specific T Cell Product Match, Were Treated Within Two Weeks of the Expected Start Date, and Received Both Weekly Doses — 86.7 Percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes (Biological); Rituximab (Biological)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Mar 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients Assigned to Arm Latent Membrane Protein-specific T-cells (LMP-TC) With Successful LMP-specific T Cell Product Match, Were Treated Within Two Weeks of the Expected Start Date, and Received Both Weekly Doses |
86.7 | — |
| SECONDARY Percentage of Patients Successfully Matched to a Latent Membrane Protein (LMP)-Specific T Cell Product Derived From a Third Party LMP-specific T Cell Bank |
— | — |
| SECONDARY Progression-free Survival |
— | — |
| SECONDARY Event-free Survival (EFS) |
— | — |
| SECONDARY Overall Survival (OS) |
— | — |
| SECONDARY Response Rate (RR) to Rituximab |
— | — |
| SECONDARY Response Rate (RR) to LMP-specific T Cells |
— | — |
| SECONDARY Absence of Epstein-Barr Virus Viremia |
— | — |
| SECONDARY Incidence of Adverse Events |
— | — |
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 = = 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 m
Data sourced from ClinicalTrials.gov (NCT02900976). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.