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

NCT02900976 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: ANHL1522NCI-2016-01110U10CA180886
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 38

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Day 1 of the first LMP-TC cycle (cycle = 42 days)

• Progression-free Survival

  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 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 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

  Up to week 3

Study Arms (2)

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.

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.

Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes; Biological: Rituximab

Interventions

Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes BIOLOGICAL

Given IV

Arm II (LMP-TC)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Arm I (RTX); Arm II (LMP-TC)

Eligibility Criteria

• Age: Up to 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (38)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Mattel Children's Hospital UCLA

Los Angeles, California, 90095, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 38163318 DERIVED

MeSH Terms

Interventions

Rituximab; CT-P10

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Birte Wistinghausen

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: September 15, 2016
• Study Start: March 22, 2017
• Primary Completion: March 31, 2021
• Study Completion: December 31, 2025
• Last Updated: January 26, 2026
• Results First Posted: June 3, 2022

Record last verified: 2026-01

Locations

US (38)