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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 17-002146
    NCT ID: NCT02900976
    Sponsor Protocol Number: ANHL1522

About this study

The purpose of this study is to assess 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. Monoclonal antibodies, such as rituximab may block tumor growth in different ways by targeting certain cells. 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 be better in treating pediatric organ recipients with post-transplant lymphoproliferative disorder than rituximab alone.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

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.
    • 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 - 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.
  • 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.
  • 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 and until six months after 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Paul Galardy, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20439036

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