Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder
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|ClinicalTrials.gov Identifier: NCT02900976|
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : October 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|CD20 Positive EBV-Related Post-Transplant Lymphoproliferative Disorder Epstein-Barr Virus Positive 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 Solid Organ Transplant Recipient||Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes Biological: Rituximab||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||March 6, 2017|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Arm I (RTX)
Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction.
Experimental: Arm II (LMP-TC)
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 cycle.
Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes
- 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 [ Time Frame: Day 42 of LMP-TC cycle 2 ]An exact one-sided binomial 95% confidence interval will be used to get a lower bound for the actual rate of successful treatments.
- 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 [ Time Frame: Day 42 of LMP-TC cycle 2 ]Will be assessed using an exact one-sided binomial 95% confidence interval to get a lower bound for the actual rate.
- Progression-free survival [ Time Frame: Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed up to 12 months ]Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
- Event-free survival (EFS) [ Time Frame: Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed up to 12 months ]Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
- Overall survival (OS) [ Time Frame: Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed up to 12 months ]Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
- Response rate (RR) to rituximab [ Time Frame: Up to week 3 ]Will be assessed using exact two-sided binomial 95% confidence intervals to get estimates of the response rate. Will be evaluated in Cohorts A and B only (combined and separately).
- Response rate (RR) to LMP-specific T cells [ Time Frame: Up to week 6 ]Will be assessed using exact two-sided binomial 95% confidence intervals to get estimates of the response rate. Will be evaluated in all Cohorts combined and in each Cohort separately.
- Absence of Epstein-Barr virus viremia [ Time Frame: Up to 12 months ]Will be correlated with RR, EFS and OS. Using the Log-Rank test for EFS and OS and the exact conditional test of proportions (Fisher?s Exact test for RR, both for all patients combined and stratified by Cohort.
- Incidence of adverse events [ Time Frame: Up to 12 months ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be described using descriptive statistics. Toxicity monitoring and analysis will be performed based on ?as treated?.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900976
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|Principal Investigator:||Birte Wistinghausen||Children's Oncology Group|