RECRUITING

Epcoritamab-CAR T Cells for Large B-cell Lymphomas

Conditions

Lymphoma, Non-Hodgkin Relapsed Diffuse Large B Cell Lymphoma Refractory Diffuse Large B-cell Lymphoma High-grade B-cell Lymphoma Transformed Indolent Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

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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 study investigates the feasibility and efficacy of epcoritamab treatment before CAR T cells. This study also investigates if, when patients have residual lymphoma after CAR T cells, epcoritamab can help to effectively treat that lymphoma.

Official Title

Phase IIa Trial to Evaluate Epcoritamab Administered Before and After CAR-T Cell Therapy in Patients With Relapsed or Refractory Large B-cell Lymphomas

Quick Facts

Study Start:2024-09-24

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06458439

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
* Age \> 18 years * Subject must be able and willing to provide informed consent. In the case where the patient is incapacitated or not otherwise capable, a legally authorized representative (or decision maker when there is not an advanced directive in place) must be willing to provide informed consent on behalf of the patient. * Able to comply with the study protocol, in the investigator's judgment * ECOG PS of 0 - 2 * Pathology report confirming eligible diagnosis * Documented CD20+ tumor cells on most recent biopsy * Patients will have failed to respond to frontline standard of care therapy containing an anthracycline and anti-CD20 antibody * Patients will be eligible and consent to be treated with a "commercially available" anti-CD19, 4-1BB, CD3zeta CAR-T cell therapy or anti-CD19, CD28, CD3zeta CAR T cell therapy (for example, tisagenlecleucel, lisocabtagene maraleucel, or axicabtagene maraleucel) * Patients must have a PET/CT scan (preferred), diagnostic CT scan, or MRI with at least one bi-dimensionally measurable lesion (≥ 1.5 cm for nodal lesions or ≥ 1cm for extra-nodal lesions in largest dimension by low-dose computerized tomography \[CT\] scan with FDG-uptake ≥ liver) * Adequate laboratory studies * Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator * Ability and willingness to take proper contraceptive precautions	* Inability or unwillingness of the patient or legally authorized representative (or decision-maker when there is not an advanced directive in place) to provide informed consent. * Prior solid organ transplantation * Primary central nervous system (CNS) lymphoma or active secondary CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) or, if clinically indicated, by lumbar puncture. * History of autoimmune disease or other diseases resulting in permanent immunosuppression or requiring chronic immunosuppressive therapy (see Exclusion Criteria 5a), with the following exceptions: 1. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone 2. Patients with a history of lymphoma-related immune thrombocytopenic purpura or autoimmune hemolytic anemia in remission may be eligible for this study if approved by the Regulatory Sponsor and Principal Investigator 3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: * Systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). However, the following are permitted: 1. If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 10 mg (or equivalent) and a total of no more than 140 mg over the last 14 days prior to the first dose of epcoritamab, unless for disease control. 2. Patients who received a single dose of a systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea or B symptoms) may be enrolled 3. The use of inhaled corticosteroids is permitted 4. The use of mineralocorticoids for management of orthostatic hypotension is permitted 5. The use of physiologic doses of corticosteroids (\< 20 mg/day of prednisone or equivalent) for uses such as management of adrenal insufficiency is permitted * Known past or current malignancy, other than inclusion diagnoses, except for: 1. Cervical carcinoma of Stage 1B or less. 2. Adequately resected, non-metastatic basal cell or squamous cell skin carcinoma. 3. Non-invasive, superficial bladder cancer. 4. Prostate cancer with a current PSA level \<0.1 ng/mL. 5. Patients with a malignancy that has been treated with curative intent will also be enrolled if that malignancy is in remission prior to first dose of epcoritamab * Known clinically significant cardiovascular disease * Patients with the following active infection(s) could have increased risks for toxicity if treated with bispecific antibody therapy, thus patient will be excluded if: 1. Positive serologic or PCR test results for acute or chronic HBV infection. Patients whose HBV infection status cannot be determined by serologic test results (www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf) must be negative for HBV by PCR to be eligible for study participation. Patients with a history of hepatitis B who are negative for HBV by PCR, will not be excluded but will be placed on suppressive antiviral therapy 2. Acute or chronic HCV infection. Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation. Patients with a history of hepatitis C who have been adequately treated (negative PCR) will not be excluded. 3. Positive serologic or RT-PCR test results for HIV infection. * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major documented infection requiring treatment with IV antibiotics or hospitalization within 2 weeks of enrollment. Empiric or prophylactic antibiotics administered during neutropenia or neutropenic fever without microbiologic evidence of infection do not exclude patients. * Clinically significant pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary disease) that requires chronic oxygen or corticosteroid use \> 20 mg mg/day prednisone or equivalent * Uncontrolled seizure disorder * Exposure to live or live attenuated vaccine within 4 weeks prior to signing ICF * Pregnancy or breast feeding * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Inclusion Criteria

Exclusion Criteria

* Age \> 18 years
* Subject must be able and willing to provide informed consent. In the case where the patient is incapacitated or not otherwise capable, a legally authorized representative (or decision maker when there is not an advanced directive in place) must be willing to provide informed consent on behalf of the patient.
* Able to comply with the study protocol, in the investigator's judgment
* ECOG PS of 0 - 2
* Pathology report confirming eligible diagnosis
* Documented CD20+ tumor cells on most recent biopsy
* Patients will have failed to respond to frontline standard of care therapy containing an anthracycline and anti-CD20 antibody
* Patients will be eligible and consent to be treated with a "commercially available" anti-CD19, 4-1BB, CD3zeta CAR-T cell therapy or anti-CD19, CD28, CD3zeta CAR T cell therapy (for example, tisagenlecleucel, lisocabtagene maraleucel, or axicabtagene maraleucel)
* Patients must have a PET/CT scan (preferred), diagnostic CT scan, or MRI with at least one bi-dimensionally measurable lesion (≥ 1.5 cm for nodal lesions or ≥ 1cm for extra-nodal lesions in largest dimension by low-dose computerized tomography \[CT\] scan with FDG-uptake ≥ liver)
* Adequate laboratory studies
* Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator
* Ability and willingness to take proper contraceptive precautions

* Inability or unwillingness of the patient or legally authorized representative (or decision-maker when there is not an advanced directive in place) to provide informed consent.
* Prior solid organ transplantation
* Primary central nervous system (CNS) lymphoma or active secondary CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) or, if clinically indicated, by lumbar puncture.
* History of autoimmune disease or other diseases resulting in permanent immunosuppression or requiring chronic immunosuppressive therapy (see Exclusion Criteria 5a), with the following exceptions:
1. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone
2. Patients with a history of lymphoma-related immune thrombocytopenic purpura or autoimmune hemolytic anemia in remission may be eligible for this study if approved by the Regulatory Sponsor and Principal Investigator
3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). However, the following are permitted:
1. If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 10 mg (or equivalent) and a total of no more than 140 mg over the last 14 days prior to the first dose of epcoritamab, unless for disease control.
2. Patients who received a single dose of a systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea or B symptoms) may be enrolled
3. The use of inhaled corticosteroids is permitted
4. The use of mineralocorticoids for management of orthostatic hypotension is permitted
5. The use of physiologic doses of corticosteroids (\< 20 mg/day of prednisone or equivalent) for uses such as management of adrenal insufficiency is permitted
* Known past or current malignancy, other than inclusion diagnoses, except for:
1. Cervical carcinoma of Stage 1B or less.
2. Adequately resected, non-metastatic basal cell or squamous cell skin carcinoma.
3. Non-invasive, superficial bladder cancer.
4. Prostate cancer with a current PSA level \<0.1 ng/mL.
5. Patients with a malignancy that has been treated with curative intent will also be enrolled if that malignancy is in remission prior to first dose of epcoritamab
* Known clinically significant cardiovascular disease
* Patients with the following active infection(s) could have increased risks for toxicity if treated with bispecific antibody therapy, thus patient will be excluded if:
1. Positive serologic or PCR test results for acute or chronic HBV infection. Patients whose HBV infection status cannot be determined by serologic test results (www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf) must be negative for HBV by PCR to be eligible for study participation. Patients with a history of hepatitis B who are negative for HBV by PCR, will not be excluded but will be placed on suppressive antiviral therapy
2. Acute or chronic HCV infection. Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation. Patients with a history of hepatitis C who have been adequately treated (negative PCR) will not be excluded.
3. Positive serologic or RT-PCR test results for HIV infection.
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major documented infection requiring treatment with IV antibiotics or hospitalization within 2 weeks of enrollment. Empiric or prophylactic antibiotics administered during neutropenia or neutropenic fever without microbiologic evidence of infection do not exclude patients.
* Clinically significant pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary disease) that requires chronic oxygen or corticosteroid use \> 20 mg mg/day prednisone or equivalent
* Uncontrolled seizure disorder
* Exposure to live or live attenuated vaccine within 4 weeks prior to signing ICF
* Pregnancy or breast feeding
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

Contacts and Locations

Study Contact

Brittany Koch

CONTACT

215-776-5548

Brittany.Koch@pennmedicine.upenn.edu

Kaitlin Kennard

CONTACT

Kaitlin.Kennard@pennmedicine.upenn.edu

Principal Investigator

Elise Chong, MD

PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at the University of Pennsylvania

Study Locations (Sites)

Abramson Cancer Center at the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Abramson Cancer Center at Penn Medicine

Elise Chong, MD, PRINCIPAL_INVESTIGATOR, Abramson Cancer Center at the University of Pennsylvania

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 Date2024-09-24

Study Completion Date2027-12

Study Record Updates

Study Start Date2024-09-24

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Lymphoma, Non-Hodgkin
Relapsed Diffuse Large B Cell Lymphoma
Refractory Diffuse Large B-cell Lymphoma
High-grade B-cell Lymphoma
Transformed Indolent Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma