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Epcoritamab Plus Standard of Care Platinum-Based Chemotherapy and Autologous Hematopoietic Cell Transplant for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

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Conditions

Recurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 RearrangementsRecurrent High Grade B-Cell Lymphoma With MYC and BCL6 RearrangementsRecurrent High Grade B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Nodal Marginal Zone LymphomaRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory High Grade B-Cell Lymphoma With MYC and BCL2 RearrangementsRefractory High Grade B-Cell Lymphoma With MYC and BCL6 RearrangementsRefractory High Grade B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Nodal Marginal Zone LymphomaRefractory Transformed Follicular 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 phase II trial tests how well epcoritamab in combination with standard of care (SOC) platinum-based chemotherapy (rituximab, ifosfamide, carboplatin, etoposide \[RICE\], rituximab, cytarabine, dexamethasone, oxaliplatin or carboplatin RDHAP/X\] or gemcitabine and oxaliplatin \[Gem/Ox\]) and autologous hematopoietic cell transplant (HCT) works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab, a type of bispecific T-cell engager, 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. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as ifosfamide, etoposide phosphate, cytarabine, and gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. An autologous HCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving epcoritamab in combination with SOC platinum-based chemotherapy, such as RICE, RDHAP/X and Gem/Ox, and autologous HCT may kill more cancer cells in patients with relapsed or refractory LBCL.

Official Title

A Phase 2 Study of Epcoritamab (Epco) Plus Physician's Choice of Platinum-Containing Chemotherapy Pre-Autologous Hematopoietic Cell Transplantation (AutoHCT) Followed by Post-AutoHCT Epco Consolidation/ Maintenance in Relapsed/ Refractory Large B-Cell Lymphoma (R/R LBCL)

Quick Facts

Study Start:2025-07-31
Study Completion:2030-08-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06905509

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 CriteriaExclusion Criteria
  1. * Participants must have histologically or cytologically confirmed R/R LBCL
  2. * Can include diffuse large B-cell lymphoma (DLBCL) (not otherwise specified \[NOS\] or with concurrent MYC and BCL2 rearrangements), high-grade B-cell lymphoma (HGBCL) (NOS or with MYC and BCL2 or BCL6 rearrangements) and transformed follicular lymphoma (FL) and nodal marginal zone lymphoma (MZL)
  3. * Histological confirmed CD20+ relapsed/ refractory large cell lymphoma
  4. * Must have had relapsed or refractory disease following standard frontline chemotherapy. Refractory disease is defined as large cell lymphoma not achieving complete remission, progressing, or relapsing within 6 months after first-line chemotherapy based on PET/CT per the Lugano criteria. Relapsed disease is defined as disease that recurs beyond 6 months after completion of initial chemotherapy based on PET/CT per the Lugano criteria
  5. * Have received 1 or more prior lines of systemic therapy for the treatment of large cell lymphoma. NOTE: Prior radiation therapy or systemic corticosteroids will not be considered a line of therapy
  6. * Candidate for platinum-containing chemotherapy (RICE, RDHAP/X, or R-Gem/Ox) pre-autologous hematopoietic cell transplantation (autoHCT) followed by autoHCT as per institutional guidelines
  7. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  8. * Measurable disease via diagnostic quality CT or PET/CT with at least 1 node having the longest diameter (LDi) greater than (\>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi \> 1 cm (per the Lugano criteria 2014)
  9. * Aged ≥ 18 at the time of consent
  10. * Creatinine clearance (CrCl) ≥ 45 mL/min (Cockcroft-Gault)
  11. * Serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
  12. * Serum aspartate aminotransferase (AST) ≤ 3 x ULN
  13. * Bilirubin ≤ 1.5 x ULN unless due to Gilbert's syndrome or controlled autoimmune hemolytic anemia (not requiring immunosuppressive other than ≤ 20 mg of prednisolone daily)
  14. * Note: Patients with Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN and direct bilirubin is ≤ 1.5 x ULN
  15. * Hemoglobin ≥ 8.0 g/dL
  16. * Note: Blood transfusion may be administered during Screening to meet this requirement only if anemia is due to marrow involvement of non-Hodgkin lymphoma (NHL)
  17. * Absolute neutrophil count ≥ 1000/uL
  18. * Note: Growth factor support is allowed to meet this requirement at Screening only if directly attributable to NHL infiltration of the bone marrow, proven by bone marrow biopsy
  19. * Platelet count ≥ 75,000/uL or ≥ 50,000/uL if bone marrow (BM) involvement or splenomegaly
  20. * Note: Transfusion may be administered during screening to meet this requirement
  21. * prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
  22. * Note: If any of the above-mentioned cytopenias are present, there should be no evidence of myelodysplastic syndrome (MDS) or hypoplastic bone marrow
  23. * HIV-infected patients on effective anti-retroviral therapy with stable viral load and CD4 count for 1 year prior to enrollment are eligible for this trial. Testing for HIV viral load and antibody at screening is mandatory
  24. * Patients with a history of chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Patients with evidence of prior HBV but who are polymerase chain reaction (PCR)-negative are permitted in the trial but should receive prophylactic antiviral therapy. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Patients who received treatment for HCV that was intended to eradicate the virus may participate if hepatitis C ribonucleic acid (RNA) levels are undetectable. Testing for HBV and HCV is mandatory at screening
  25. * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 12 months after the last dose of epcoritamab
  26. * Provision of signed and dated informed consent form
  1. * Any adverse event (AE) related to the previous large cell lymphoma therapy which has not recovered to grade ≤ 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0) or baseline by cycle 1 day 1 (C1D1), except alopecia and non-clinically significant laboratory abnormalities
  2. * Uncontrolled intercurrent illness (including infection)
  3. * Known active central nervous system or meningeal (including leptomeningeal) involvement. Patients diagnosed with central nervous system (CNS) disease who achieved and maintained CNS complete response (CR) at the time of relapse are eligible. Lumbar puncture must be done in this case prior to study entry (within 90 days of enrollment) to demonstrate CNS CR status. Tests to investigate CNS involvement are required otherwise only if clinically indicated (i.e. disease suspected on basis of symptoms or other findings)
  4. * Receiving any other investigational treatments
  5. * Previous treatment with any bispecific T-cell engager with or without chemotherapy
  6. * Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to the first dose of epcoritamab
  7. * Concurrent use of other anti-cancer agents or treatments except for certain therapeutics (e.g., prostate, breast hormonal-based therapy) per the treating physician's discretion
  8. * Standard agents within 2 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab (excluding anti-CD20 monoclonal antibodies \[mAbs\], which can be administered until first full dose of epcoritamab); or
  9. * CAR-T cell therapy within 30 days prior to the first dose of epcoritamab
  10. * Palliative radiation is permitted only if on non-target lesions
  11. * Motor and sensory neuropathy grade ≥ 2 (CTCAE v.5.0)
  12. * Patients with a history of other malignancies, except adequately treated non-melanoma skin cancer, non-invasive superficial bladder cancer, curatively treated in-situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, localized low grade prostate cancer (up to Gleason score 6), or other solid tumors curatively treated with no evidence of disease for at least 3 years
  13. * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at trial enrollment or significant infections within 2 weeks prior to the first dose of epcoritamab
  14. * Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy. Low-dose (10 mg/day) prednisolone (or equivalent) for rheumatoid arthritis or similar conditions is allowed
  15. * Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
  16. * Participant received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation
  17. * Autoimmune disease or other diseases that require continuous immunosuppressive therapy (except for prednisone doses of less than or equal to 10 mg, which is allowed)
  18. * Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia (requiring \> 20 mg of prednisolone daily) or other concurrent uncontrolled medical conditions
  19. * Clinically significant cardiac disease including but not limited to:
  20. * Unstable or uncontrolled disease/condition related to or affecting cardiac function, e.g., unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association, uncontrolled clinically significant cardiac arrhythmia (CTCAE v 5.0 grade 2 or higher), or clinically significant electrocardiogram (ECG) abnormalities. Controlled New York Heart Association (NYHA) grade 1 or 2 are eligible
  21. * Myocardial infarction, intracranial bleed, or stroke within the past 6 months
  22. * Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \> 480 msec. NOTE: This criterion does not apply to participants with a left bundle branch block
  23. * In case of any history of cardiovascular disease, a cardiology consult is required within 60 days prior to enrollment
  24. * Age ≥ 75 and 2 or more active grade ≥ 2 cardiovascular conditions
  25. * Prior treatment with live, attenuated vaccines within 28 days prior to initiation of epcoritamab. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Food and Drug Administration (FDA)-approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations allowed
  26. * Immune effector cell encephalopathy (ICE) score of less than 10 at study entry
  27. * Suspected allergies, hypersensitivity, or intolerance to epcoritamab or another anti-CD20 mAb or its excipients
  28. * Active HBV (DNA PCR-positive). Patients with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy
  29. * Active hepatitis C (RNA PCR-positive infection). Patients who received treatment for HCV that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable
  30. * Known history of seropositivity for HIV infection
  31. * Active cytomegalovirus (CMV) infection (PCR positive)
  32. * Pregnant, breastfeeding, or planning to become pregnant while enrolled in this trial or within 12 months after the last dose of epcoritamab
  33. * Plans to donate sperm or conceive a child through intercourse while enrolled in this trial or within 12 months after the last dose of epcoritamab
  34. * Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the first dose of epcoritamab
  35. * Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or have had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection. Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen per criteria
  36. * Suspected active or inadequately treated latent tuberculosis

Contacts and Locations

Study Contact

Selina Laqui
CONTACT
916-734-0565
sblaqui@ucdavis.edu

Principal Investigator

Joseph M Tuscano
STUDY_CHAIR
University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
United States

Collaborators and Investigators

Sponsor: University of California, Davis

  • Joseph M Tuscano, STUDY_CHAIR, University of California, Davis

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 Date2025-07-31
Study Completion Date2030-08-01

Study Record Updates

Study Start Date2025-07-31
Study Completion Date2030-08-01

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements
  • Recurrent High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements
  • Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Recurrent Nodal Marginal Zone Lymphoma
  • Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Refractory High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements
  • Refractory High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements
  • Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Refractory Nodal Marginal Zone Lymphoma
  • Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma