RECRUITING

Epcoritamab for the Treatment of Relapsed or Refractory Post Transplant Lymphoproliferative Disorders

Conditions

Diffuse Large B-Cell Lymphoma Post-Transplant Lymphoproliferative Disorder EBV-Related 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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase Ib trial tests the safety and effectiveness of epcoritamab in treating patients with post-transplant lymphoproliferative disorder (PTLD) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Giving epcoritamab may be safe and effective in treating patients with relapsed or refractory B-cell PTLD.

Official Title

Phase Ib Study to Assess the Efficacy and Safety of Epcoritamab in Relapsed or Refractory Post-Transplant Lymphoproliferative Disorder

Quick Facts

Study Start:2025-01-01

Study Completion:2026-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06672705

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information to the sponsor, sites, and relevant study organizations. * Age ≥ 18 years at the time of consent. * Karnofsky scale ≥ 50% or Eastern Cooperative Oncology Group (ECOG) ≤ 2. * Histological evidence of B-cell PTLD (any histologic subtype) following solid organ transplantation; expresses CD20; with or without EBV association. * Treatment failure of immunosuppression reduction (ISR). NOTE: if ISR was deemed not feasible by treating physician, ISR treatment failure may be waived. * Treatment failure of rituximab or rituximab plus any concurrent or sequentially administered chemotherapy regimen. * Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement. * Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned. * HIV infection is allowed if viral load is undetectable at time of enrollment, CD4+ count \> 200 cells/uL, and subject remains on anti-viral therapy. * Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator. * Expected survival greater than 60 days. * Absolute neutrophil count 1.0 ≥ x 10\^9/L. * Platelets 50 ≥ x 10\^9/L. * Creatinine clearance (mL/min) ≥ 30 mL/min - Cockcroft-Gault Equation. * Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy. * Bilirubin ≤ 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 3.0 mg/dL if their conjugated bilirubin is ≤ 3.0 × ULN). * Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy. * Aspartate aminotransferase (AST) ≤ 3.0 x ULN. * Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy. * Alanine aminotransferase (ALT) ≤ 3.0 x ULN. * Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy. * Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. * Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of epcoritamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device. * Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of epcoritamab. * Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial. * Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.	* Uncontrolled active (symptomatic) infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator. * Post-transplant lymphoproliferative disorder following stem cell transplantation for hematologic malignancies or nonmalignant conditions. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drug). * Subjects with central nervous system (CNS) involvement by PTLD. * Seizure disorder requiring therapy (such as steroids or anti-epileptics). * Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure \> 180mmHg or diastolic blood pressure \> 120mmHg). * History of progressive multifocal leukoencephalopathy. * Active Hepatitis B infection or Hepatitis C infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active Hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression. Subjects with history of Hepatitis C infection (undetectable viral PCR) are allowed. * Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant. * Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study. * Live virus vaccines must not be administered within 28 days of the start of study treatment. * Any investigational treatments must have been completed at least 4 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. Investigational antibody therapies are not included in this requirement.

Inclusion Criteria

Exclusion Criteria

* Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information to the sponsor, sites, and relevant study organizations.
* Age ≥ 18 years at the time of consent.
* Karnofsky scale ≥ 50% or Eastern Cooperative Oncology Group (ECOG) ≤ 2.
* Histological evidence of B-cell PTLD (any histologic subtype) following solid organ transplantation; expresses CD20; with or without EBV association.
* Treatment failure of immunosuppression reduction (ISR). NOTE: if ISR was deemed not feasible by treating physician, ISR treatment failure may be waived.
* Treatment failure of rituximab or rituximab plus any concurrent or sequentially administered chemotherapy regimen.
* Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement.
* Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned.
* HIV infection is allowed if viral load is undetectable at time of enrollment, CD4+ count \> 200 cells/uL, and subject remains on anti-viral therapy.
* Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator.
* Expected survival greater than 60 days.
* Absolute neutrophil count 1.0 ≥ x 10\^9/L.
* Platelets 50 ≥ x 10\^9/L.
* Creatinine clearance (mL/min) ≥ 30 mL/min - Cockcroft-Gault Equation.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Bilirubin ≤ 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 3.0 mg/dL if their conjugated bilirubin is ≤ 3.0 × ULN).
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN.
* Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.
* Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
* Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of epcoritamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device.
* Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of epcoritamab.
* Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial.
* Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.

* Uncontrolled active (symptomatic) infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator.
* Post-transplant lymphoproliferative disorder following stem cell transplantation for hematologic malignancies or nonmalignant conditions.
* Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drug).
* Subjects with central nervous system (CNS) involvement by PTLD.
* Seizure disorder requiring therapy (such as steroids or anti-epileptics).
* Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure \> 180mmHg or diastolic blood pressure \> 120mmHg).
* History of progressive multifocal leukoencephalopathy.
* Active Hepatitis B infection or Hepatitis C infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active Hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression. Subjects with history of Hepatitis C infection (undetectable viral PCR) are allowed.
* Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
* Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study.
* Live virus vaccines must not be administered within 28 days of the start of study treatment.
* Any investigational treatments must have been completed at least 4 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. Investigational antibody therapies are not included in this requirement.

Contacts and Locations

Study Contact

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Principal Investigator

Timothy J Voorhees, MD

PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Study Locations (Sites)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Collaborators and Investigators

Sponsor: Timothy Voorhees

Timothy J Voorhees, MD, PRINCIPAL_INVESTIGATOR, Ohio State University Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-01

Study Completion Date2026-12-31

Study Record Updates

Study Start Date2025-01-01

Study Completion Date2026-12-31

Terms related to this study

Additional Relevant MeSH Terms

Diffuse Large B-Cell Lymphoma Post-Transplant Lymphoproliferative Disorder
EBV-Related 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