EBV-Related Post-Transplant Lymphoproliferative DisorderPhase 2NCT02900976
Rituximab and LMP-Specific T-Cells in Treating Pediatric Solid Organ Recipients With EBV-Positive, CD20-Positive Post-Transplant Lymphoproliferative Disorder
A Phase 2 study testing Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes and Rituximab in people with EBV-Related Post-Transplant Lymphoproliferative Disorder and Monomorphic Post-Transplant Lymphoproliferative Disorder, run by Children's Oncology Group at 38 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 29 years
- Conditions the study is for
- EBV-Related Post-Transplant Lymphoproliferative Disorder, Monomorphic Post-Transplant Lymphoproliferative Disorder, Polymorphic Post-Transplant Lymphoproliferative Disorder
- What is being tested?
- Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 38 sitesUnited States
- Study dates
- 22 Mar 2017to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient must have a history of solid organ transplantation
- Patients must have biopsy-proven newly diagnosed, relapsed or refractory polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is:
- CD20 positive
- EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ hybridization (preferred) and/or LMP immunoperoxidase staining
- There must be evaluable disease at study entry either by imaging or by serial endoscopic biopsies.
- Note: a measurable node must have an LDi (longest diameter) greater than 1.5 cm; a measurable extranodal lesion should have an LDi greater than 1.0 cm; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
Show all 20Show fewer
- Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1
- Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- Patients must have a life expectancy of >= 8 weeks
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study
- COHORT A and B: Patient must not have received therapy with anti-CD20 monoclonal antibodies within 90 days of entry onto this study
- COHORT C: Patient must have received rituximab at 375 mg/m^2 weekly for at least 3 doses within the last 90 days prior to study enrollment
- Must not have received any prior radiation to any sites of measurable disease
- Must not have received any prior stem cell transplant
- Must not have received investigational therapy within 30 days of entry onto this study
- Must not have received prior EBV or LMP-specific T cells within 90 days of entry onto this study
- Must not have received alemtuzumab or other anti-T-cell antibody therapy within 28 days of entry onto this study
- COHORT C: HLA typing is available and will be submitted at the time of enrollment.
Who cannot join
- Burkitt morphology
- Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar puncture
- Note: lumbar puncture can be performed at the time of diagnosis and does not need to be repeated unless there is a change in neurological status or it was performed more than 14 days prior to study entry
- Bone marrow involvement (> 25%)
- Note: bone marrow aspiration/biopsy can be performed at the time of diagnosis and does not need to be repeated unless there is a change in peripheral blood counts or it was performed more than 14 days prior to study entry
- Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following:
Show all 19Show fewer
- Bone marrow (including pancytopenia without any detectable B-cell proliferation)
- Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)
- Lungs (interstitial pneumonitis with or without pleural effusions)
- Gastrointestinal hemorrhage
- Any documented donor-derived PTLD
- Hepatitis B or C serologies consistent with past or current infections because of the risk of reactivation with rituximab
- Severe and/or symptomatic refractory concurrent infection other than EBV
- Pregnant females are ineligible since there is no available information regarding human fetal or teratogenic toxicities
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 12 months following completion of study therapy.
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
United States38 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Children's Hospital of Alabama
Birmingham, Alabama, 35233
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Loma Linda University Medical Center
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Primary Children's Hospital
Salt Lake City, Utah, 84113
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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.
- 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
- Being tested
- Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes, Rituximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic LMP1/LMP2-Specific Cytotoxic T-LymphocytesBiological
Given IV
RituximabBiological
Also called ABP 798, ABP-798, ABP798, BI 695500
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (RTX) | Experimental | Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction. Receives: Biological: Rituximab |
| Arm II (LMP-TC) | Experimental | 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. Receives: Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: Day 8 of the first LMP-TC cycle (cycle = 42 days)
Secondary outcomes (8)
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
Will be assessed using an exact one-sided binomial 95% confidence interval to get a lower bound for the actual rate.
Measured: Day 1 of the first LMP-TC cycle (cycle = 42 days)
Progression-free Survival
Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Measured: 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
Event-free Survival (EFS)
Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Measured: 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
Overall Survival (OS)
Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.
Measured: 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
Response Rate (RR) to Rituximab
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).
Measured: Up to week 3
Response Rate (RR) to LMP-specific T Cells
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.
Measured: Up to week 6
Absence of Epstein-Barr Virus Viremia
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.
Measured: Up to 12 months
Incidence of Adverse Events
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".
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2016 (estimated)
- Study start22 Mar 2017
- Primary completion31 Mar 2021
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EBV-Related Post-Transplant Lymphoproliferative DisorderStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Birte Wistinghausen, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02900976
- Sponsor's protocol ID
- ANHL1522
- Other IDs
- NCI-2016-01110, ANHL1522, ANHL1522, ANHL1522, U10CA180886
- Status last verified
- Jan 2026
- First submitted
- 6 Sep 2016
- Last updated
- 26 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wistinghausen B, Toner K, Barkauskas DA, Jerkins LP, Kinoshita H, Chansky P, Pezzella G, Saguilig L, Hayashi RJ, Abhyankar H, Scull B, Karri V, Tanna J, Hanley P, Hermiston ML, Allen CE, Bollard CM. Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children's Oncology Group study. Blood Adv. 2024 Mar 12;8(5):1116-1127. doi: 10.1182/bloodadvances.2023010832.
PubMed 38163318
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02900976
- Acronym / sponsor ID
- ANHL1522
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 22 Mar 2017 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 15 Sep 2016 (estimated)
- Results
- Posted 3 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (RTX) | Experimental | Biological: RituximabPatients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction. |
| Arm II (LMP-TC) | Experimental | Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes, Biological: RituximabPatients 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. |
Who may qualify
- Ages
- Up to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Patient must have a history of solid organ transplantation
- Patients must have biopsy-proven newly diagnosed, relapsed or refractory polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is:
- There must be evaluable disease at study entry either by imaging or by serial endoscopic biopsies.
- Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1
Key exclusion criteria (19 listed)
- Burkitt morphology
- Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar puncture
- Bone marrow involvement (> 25%)
- Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following:
- Any documented donor-derived PTLD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic LMP1/LMP2-Specific Cytotoxic T-LymphocytesGiven IV | Biological | Arm II (LMP-TC) |
| RituximabAlso: ABP 798, ABP-798, ABP798, BI 695500Given IV | Biological | Arm I (RTX), Arm II (LMP-TC) |
Primary outcome
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 8 of the first LMP-TC cycle (cycle = 42 days)
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.
8 secondary outcomes
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 1 of the first LMP-TC cycle (cycle = 42 days)
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 12 months from enrollment of the last patient on the study
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 12 months from enrollment of the last patient on the study
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 12 months from enrollment of the last patient on the study
Response Rate (RR) to Rituximab
Time frame: Up to week 3
Response Rate (RR) to LMP-specific T Cells
Time frame: Up to week 6
Absence of Epstein-Barr Virus Viremia
Time frame: Up to 12 months
Incidence of Adverse Events
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38163318Wistinghausen B, Toner K, Barkauskas DA, Jerkins LP, Kinoshita H, Chansky P, Pezzella G, Saguilig L, Hayashi RJ, Abhyankar H, Scull B, Karri V, Tanna J, Hanley P, Hermiston ML, Allen CE, Bollard CM. Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children's Oncology Group study. Blood Adv. 2024 Mar 12;8(5):1116-1127. doi: 10.1182/bloodadvances.2023010832.
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Diffuse Large B-Cell Lymphoma Post-Transplant Lymphoproliferative Disorder, EBV-Related Post-Transplant Lymphoproliferative Disorder
RecruitingPhase 1
BZLF1 Peptide Vaccine (OSU-2131) With QS-21 for the Prevention of Epstein-Barr Virus Related Cancer in Patients Awaiting Solid Organ Transplants
Chronic Kidney Disease, Stage 4, Chronic Kidney Disease, Stage 5
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Birte Wistinghausen principal investigator
Children's Oncology Group
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes and Rituximab in people with EBV-Related Post-Transplant Lymphoproliferative Disorder and Monomorphic Post-Transplant Lymphoproliferative Disorder, run by Children's Oncology Group at 38 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 8 of the first LMP-TC cycle (cycle = 42 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02900976, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026; AzTrials last refreshed its copy on 6 Nov 2026.