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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (RTX) Arm II (LMP-TC)
Hide 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
Arm/Group Title Arm I (RTX) Arm II (LMP-TC) Total
Hide 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
Hide 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
2 16 18
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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)
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Progression-free Survival
Hide Description Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Time Frame Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed 12 months from enrollment of the last patient on the study
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Time Frame Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed 12 months from enrollment of the last patient on the study
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Time Frame Time to first occurrence of progression or death (events) or loss to follow-up or survival to analysis date (non-events), assessed 12 months from enrollment of the last patient on the study
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Response Rate (RR) to Rituximab
Hide Description 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).
Time Frame Up to week 3
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Response Rate (RR) to LMP-specific T Cells
Hide Description 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.
Time Frame Up to week 6
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Absence of Epstein-Barr Virus Viremia
Hide Description Will be correlated with response rate (RR), event-free survival (EFS) and overall survival (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.
Time Frame Up to 12 months
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Incidence of Adverse Events
Hide Description 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".
Time Frame Up to 12 months
Outcome Measure Data Not Reported
Time Frame Enrollment up to 5 years after enrollment
Adverse Event Reporting Description The SAE table reflects NCI CTCAEs submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Not every patient from Arm LMPTC received induction therapy (refractory patients are excluded), so the denominator for Arm LMPTC Induction is less than the denominator for Arm LMPTC
 
Arm/Group Title Arm I (RTX) Induction Arm II (LMP-TC) Induction Arm I (RTX) Arm II (LMP-TC)
Hide Arm/Group Description 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 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 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

All-Cause Mortality
Arm I (RTX) Induction Arm II (LMP-TC) Induction Arm I (RTX) Arm II (LMP-TC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   1/11 (9.09%)   0/2 (0.00%)   3/15 (20.00%) 
Hide Serious Adverse Events
Arm I (RTX) Induction Arm II (LMP-TC) Induction Arm I (RTX) Arm II (LMP-TC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   0/11 (0.00%)   0/2 (0.00%)   6/15 (40.00%) 
Cardiac disorders         
Cardiac disorders - Other, specify   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  3/15 (20.00%) 
General disorders         
Death NOS   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  2/15 (13.33%) 
Fever   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Immune system disorders         
Cytokine release syndrome   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  3/15 (20.00%) 
Infections and infestations         
Infections and infestations - Other, specify   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Investigations         
Neutrophil count decreased   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders         
Hypoxia   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (RTX) Induction Arm II (LMP-TC) Induction Arm I (RTX) Arm II (LMP-TC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   5/11 (45.45%)   1/2 (50.00%)   3/15 (20.00%) 
Blood and lymphatic system disorders         
Anemia   1/2 (50.00%)  2/11 (18.18%)  0/2 (0.00%)  0/15 (0.00%) 
Eosinophilia   0/2 (0.00%)  0/11 (0.00%)  1/2 (50.00%)  0/15 (0.00%) 
Febrile neutropenia   1/2 (50.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders         
Abdominal pain   0/2 (0.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
Constipation   0/2 (0.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
Diarrhea   0/2 (0.00%)  0/11 (0.00%)  1/2 (50.00%)  0/15 (0.00%) 
Ileus   0/2 (0.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
Nausea   0/2 (0.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
Vomiting   1/2 (50.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
General disorders         
Fever   1/2 (50.00%)  0/11 (0.00%)  0/2 (0.00%)  0/15 (0.00%) 
Infections and infestations         
Catheter related infection   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Infections and infestations - Other, specify   1/2 (50.00%)  0/11 (0.00%)  0/2 (0.00%)  0/15 (0.00%) 
Investigations         
GGT increased   0/2 (0.00%)  0/11 (0.00%)  1/2 (50.00%)  0/15 (0.00%) 
Lymphocyte count decreased   1/2 (50.00%)  4/11 (36.36%)  0/2 (0.00%)  0/15 (0.00%) 
Neutrophil count decreased   2/2 (100.00%)  1/11 (9.09%)  0/2 (0.00%)  1/15 (6.67%) 
White blood cell decreased   1/2 (50.00%)  2/11 (18.18%)  0/2 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders         
Dehydration   1/2 (50.00%)  0/11 (0.00%)  0/2 (0.00%)  0/15 (0.00%) 
Hyperkalemia   0/2 (0.00%)  2/11 (18.18%)  0/2 (0.00%)  0/15 (0.00%) 
Hypocalcemia   1/2 (50.00%)  0/11 (0.00%)  0/2 (0.00%)  0/15 (0.00%) 
Hypokalemia   1/2 (50.00%)  2/11 (18.18%)  0/2 (0.00%)  0/15 (0.00%) 
Vascular disorders         
Flushing   0/2 (0.00%)  1/11 (9.09%)  0/2 (0.00%)  0/15 (0.00%) 
Hematoma   0/2 (0.00%)  0/11 (0.00%)  0/2 (0.00%)  1/15 (6.67%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior sponsor approval
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 16264470064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02900976    
Other Study ID Numbers: ANHL1522
NCI-2016-01110 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ANHL1522
ANHL1522 ( Other Identifier: Children's Oncology Group )
ANHL1522 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Submitted: September 6, 2016
First Posted: September 15, 2016
Results First Submitted: March 4, 2022
Results First Posted: June 3, 2022
Last Update Posted: June 3, 2022