Polymorphic Post-Transplant Lymphoproliferative Disorder Clinical Trial
Official title:
A Pilot Study of Rituximab (RTX) and Third Party Latent Membrane Protein (LMP)-Specific Cytotoxic T-Lymphocytes (LMP-TC) in Pediatric Solid Organ Recipients (SOT) With EBV-Positive CD20-Positive Post-Transplant Lymphoproliferative Disease (PTLD)
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.
PRIMARY OBJECTIVE: I. To determine the feasibility of treating pediatric and young adult solid organ transplant recipients who have newly diagnosed, relapsed or refractory Epstein-Barr virus (EBV)-positive CD20-positive post-transplant lymphoproliferative disease (PTLD) with a novel T-cell therapeutic, allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes (third party latent membrane protein [(LMP]-)]-specific T cells), in a cooperative group setting. SECONDARY OBJECTIVES: I. To determine the percentage of eligible patients for whom a suitable LMP-specific T-cell product derived from a third party LMP-specific T-cell bank is available. II. To estimate the response rate (RR) to three doses of rituximab (RTX) as single agent in children and young adults with newly diagnosed or relapsed EBV-positive CD20-positive PTLD after solid organ transplantation (SOT). III. To estimate the 2-year event-free survival (EFS) of children and young adults with newly diagnosed, refractory or relapsed EBV-positive CD20-positive PTLD after SOT treated with RTX and/or LMP-specific T cells. IV. To estimate overall survival (OS) of children and young adults with newly diagnosed, refractory or relapsed EBV-positive CD20-positive PTLD after SOT treated with RTX and/or LMP-specific T cells. V. To estimate the RR to LMP-specific T cells of newly diagnosed (without complete response to course RTX1), refractory, and relapsed children and young adults with EBV-positive CD20-positive PTLD. VI. To estimate progression-free survival (PFS) of children and young adults with newly diagnosed, refractory or relapsed EBV-positive CD20-positive PTLD after SOT treated with RTX and/or LMP-specific T cells. VII. To describe the toxicity of third party LMP-specific T cells in children and young adults with newly diagnosed, refractory or relapsed EBV-positive CD20-positive PTLD after SOT treated with RTX and/or LMP-specific T cells. VIII. To validate that absence of EBV viremia correlates with RR, EFS and OS. EXPLORATORY OBJECTIVES: I. To determine whether third party LMP-specific T cells promote autologous immune reconstitution of EBV-specific T cells. II. To determine whether EBV viremia is inversely correlated with an increase in EBV-specific T cells in vivo. III. To determine whether plasma cytokine profile and changes in cytokines over time correlate with treatment response or toxicity (e.g. cytokine release syndrome). OUTLINE: INDUCTION (Cohorts A and B): Patients receive rituximab or biosimilar intravenously (IV) on days 1, 8, 15. Cycle continues for up to 21 days in the absence of disease progression or unacceptable toxicity. Patients are assigned to 1 of 2 arms. ARM I (RTX, Cohorts A): Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction. ARM II (LMP-TC, Cohorts A, B, C): Patients with newly diagnosed PTLD who do not achieve a CR to induction, all relapsed patients after induction, and all patients with refractory disease who received rituximab or biosimilar within 90 days according to institutional guidelines, receive allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes IV over 1- 2 minutes on days 0 and 7. Cycle continues for up to 42 days in the absence of disease progression or unacceptable toxicity. Patients with PR or SD after first cycle of cycle allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes receive an additional course. After completion of study treatment, patients are followed up at 1, 2, 3, 6, 9, and 12 months. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05786040 -
Tafasitamab and Rituximab for Front-Line Treatment of Post-Transplant Lymphoproliferative Disorder
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Phase 2 |