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 : Active, not recruiting

First Posted : September 15, 2016

Results First Posted : June 3, 2022

Last Update Posted : June 3, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	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
Interventions	Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes Biological: Rituximab
Enrollment	18

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm I (RTX)	Arm II (LMP-TC)
Arm/Group Description	Patients with newly diagnosed PTLD ...	Patients with newly diagnosed PTLD ...
Arm/Group Description	Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction. Rituximab: Given IV	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. Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes: Given IV Rituximab: Given IV
Period Title: Overall Study
Started	2	16
Completed	2	7
Not Completed	0	9
Reason Not Completed
Adverse Event	0	1
Physician Decision	0	2
Progressive disease	0	6

Baseline Characteristics

Arm/Group Title		Arm I (RTX)	Arm II (LMP-TC)	Total
Arm/Group Description		Patients with newly diagnosed PTLD ...	Patients with newly diagnosed PTLD ...	Total of all reporting groups
Arm/Group Description		Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction. Rituximab: Given IV	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. Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes: Given IV Rituximab: Given IV	Total of all reporting groups
Overall Number of Baseline Participants		2	16	18
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2 participants	16 participants	18 participants
	<=18 years	2 100.0%	14 87.5%	16 88.9%
	Between 18 and 65 years	0 0.0%	2 12.5%	2 11.1%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	2 participants	16 participants	18 participants
		6 (7.1)	10.1 (6.4)	9.6 (6.4)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2 participants	16 participants	18 participants
	Female	2 100.0%	6 37.5%	8 44.4%
	Male	0 0.0%	10 62.5%	10 55.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2 participants	16 participants	18 participants
	Hispanic or Latino	1 50.0%	3 18.8%	4 22.2%
	Not Hispanic or Latino	1 50.0%	11 68.8%	12 66.7%
	Unknown or Not Reported	0 0.0%	2 12.5%	2 11.1%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2 participants	16 participants	18 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 6.3%	1 5.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 50.0%	4 25.0%	5 27.8%
	White	1 50.0%	8 50.0%	9 50.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	3 18.8%	3 16.7%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	2 participants	16 participants	18 participants
United States		2	16	18

Outcome Measures

1.Primary Outcome


Title	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
Description	The percentage of patients assigned to Arm LMP-TC who had a suitable L...
Description	The percentage of patients assigned to Arm LMP-TC who had a suitable LMP-specific T-cell product, were treated within two weeks of the expected start date, and received both weekly doses in a cooperative multi-institutional setting. A statistical analysis was planned, but not performed because accrual was stopped early and the sample size required for the analysis was not reached.
Time Frame	Day 8 of the first LMP-TC cycle (cycle = 42 days)

Outcome Measure Data

Analysis Population Description

2 Arm I (RTX) patients and 1 Arm II (LMP-TC) patient who came off protocol therapy prior to Callback were excluded from this analysis.


Arm/Group Title	Arm II (LMP-TC)
Arm/Group Description:	Patients with newly diagnosed PTLD ...
Arm/Group Description:	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. Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes: Given IV Rituximab: Given IV
Overall Number of Participants Analyzed	15
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of patients
	86.7 (59.5 to 98.3)

2.Secondary Outcome


Title	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
Description	Will be assessed using an exact one-sided binomial 95% confidence inte...
Description	Will be assessed using an exact one-sided binomial 95% confidence interval to get a lower bound for the actual rate.
Time Frame	Day 1 of the first LMP-TC cycle (cycle = 42 days)