Clinical Trial: Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive Cluster of Differentiation(CD) 20-Positive Post-Transplant Lymphoproliferative Disorder

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Pilot Study of Rituximab (RTX) and Third Party Latent Membrane Protein (LMP)-Specific Cytotoxic T-Lymphocytes in Pediatric Solid Organ Recipients (SOT) With EBV-Positive CD20-Positive PRIMARY OBJECTIVES:

I. To determine the feasibility of treating pediatric and young adult solid organ transplant recipients with newly diagnosed or recurrent Epstein-Barr virus (EBV)-positive CD20-positive post-transplant lymphoproliferative disease (PTLD) with a novel T cell therapeutic, allogeneic Latent Membrane Protein(LMP)1/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 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 EBV-positive CD20-positive PTLD after SOT treated with RTX with/without LMP-specific T cells.

IV. To estimate overall survival (OS) of children and young adults with EBV-positive CD20-positive PTLD after SOT treated with RTX with/without LMP-specific T cells.

V. To estimate the RR to LMP-specific T cells of children and young adults with EBV-positive CD20-positive PTLD after SOT who have not had a complete response to RTX.

VI. To estimate progression-free survival (PFS) of children and young adults with EBV-positive CD20-positive PTLD after SOT treated with RTX with/without LMP-specific T cells.

An exact one-sided binomial 95% confidence interval will be used to get a lower bound for the actual rate of successful treatments.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Absence of EBV 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 for RR.
  • 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.
  • Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events [ Time Frame: Up to 12 months ]
    Toxicities will be described using descriptive statistics. Toxicity monitoring and analysis will be performed based on "as treated".
  • 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.
  • Percentage of patients successfully matched to a LMP-specific T cell product derived from a third party LMP-specific T cell bank [ Time Frame: Day 42 of LMP-TC course 2 ]
    Will be assessed using an exact one-sided binomial 95% confidence interval to get a lower bound for the actual rate.
  • PFS [ 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.
  • 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.
  • 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.


Original Secondary Outcome: Same as current

Information By: Children's Oncology Group

Dates:
Date Received: September 6, 2016
Date Started: March 6, 2017
Date Completion: December 2021
Last Updated: April 24, 2017
Last Verified: April 2017