Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder

Completed · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT02900976
Run by: Children's Oncology Group
People needed: 18
Starts: 2017-03-22
Expected to finish: 2025-12-31
Last updated by the study team: 2026-01-26

Who can join

Age: any, up to 29. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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

Where it is running

Children's Hospital of Alabama — Birmingham, Alabama, United States
Phoenix Childrens Hospital — Phoenix, Arizona, United States
Loma Linda University Medical Center — Loma Linda, California, United States
Children's Hospital Los Angeles — Los Angeles, California, United States
Mattel Children's Hospital UCLA — Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
UCSF Medical Center-Mission Bay — San Francisco, California, United States
Children's Hospital Colorado — Aurora, Colorado, United States
Children's National Medical Center — Washington D.C., District of Columbia, United States
UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
Riley Hospital for Children — Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
C S Mott Children's Hospital — Ann Arbor, Michigan, United States
University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States
Mayo Clinic in Rochester — Rochester, Minnesota, United States
University of Mississippi Medical Center — Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
Washington University School of Medicine — St Louis, Missouri, United States
University of Nebraska Medical Center — Omaha, Nebraska, United States
Hackensack University Medical Center — Hackensack, New Jersey, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
University of Rochester — Rochester, New York, United States

Full record on ClinicalTrials.gov

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