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Trial record 1 of 1 for:    ANHL1522
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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

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ClinicalTrials.gov Identifier: NCT02900976
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : November 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

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. Immunotherapy with monoclonal antibodies, such as rituximab, may induce changes in the body's immune system and may interfere with the ability of tumor 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.

Condition or disease Intervention/treatment Phase
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 Biological: Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes Biological: Rituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 6, 2017
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Arm I (RTX)
Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction.
Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab ABBS
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • rituximab biosimilar TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima

Experimental: Arm II (LMP-TC)
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
Given IV

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab ABBS
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar JHL1101
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • rituximab biosimilar TQB2303
  • rituximab-abbs
  • RTXM83
  • Truxima




Primary Outcome Measures :
  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 [ Time Frame: Day 8 of the first LMP-TC cycle (cycle = 42 days) ]
    An exact one-sided binomial 95% confidence interval will be used to get a lower bound for the actual rate of successful treatments.


Secondary Outcome Measures :
  1. 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) ]
    Will be assessed using an exact one-sided binomial 95% confidence interval to get a lower bound for the actual rate.

  2. 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 up to 12 months ]
    Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.

  3. 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 up to 12 months ]
    Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.

  4. 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 up to 12 months ]
    Will be assessed using Kaplan-Meier estimates, for all patients combined and separately for each cohort.

  5. 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. Will be evaluated in Cohorts A and B only (combined and separately).

  6. Response rate (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. Will be evaluated in all Cohorts combined and in each Cohort separately.

  7. Absence of Epstein-Barr virus 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 (Fisher's Exact test for RR, both for all patients combined and stratified by Cohort.

  8. Incidence of adverse events [ Time Frame: Up to 12 months ]
    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".



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900976


  Show 38 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Birte Wistinghausen Children's Oncology Group

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02900976     History of Changes
Other Study ID Numbers: ANHL1522
NCI-2016-01110 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ANHL1522
ANHL1522 ( Other Identifier: Childrens Oncology Group )
ANHL1522 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: September 15, 2016    Key Record Dates
Last Update Posted: November 27, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoproliferative Disorders
Disease
Pathologic Processes
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents