Epcoritamab in Combination With R-CHOP Debulking in Newly Diagnosed Patients With Aggressive Non-Hodgkin Lymphoma

Official Summary

A Phase II, open-label, two-arm, multicenter study evaluating the combination of epcoritamab with R-CHOP chemotherapy in patients with newly diagnosed, aggressive B-cell non-Hodgkin lymphoma.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 20 participants

Study Arms

• Arm A: Treatment with Standard Dexamethasone (First 6 participants) (EXPERIMENTAL)
  Participants will receive 8 cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone (R-CHOP) chemotherapy combined with epcoritamab. A standard dose of dexamethasone is given in Cycle 2. Treatment includes six 21-day cycles: Cycle 1 consists of R-CHOP alone; Cycles 2-5 include R-CHOP on Day 1 with epcoritamab on Days 1, 8, and 15. In Cycle 2, dexamethasone is given on epcoritamab treatment days and for 3 subsequent days. In Cycle 6, both R-CHOP and epcoritamab are given
• Arm B: Treatment with Modified Dexamethasone (EXPERIMENTAL)
  Participants will receive 8 cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone (R-CHOP) chemotherapy combined with epcoritamab. A modified dose of dexamethasone will be given in Cycle 2. Treatment includes six 21-day cycles: Cycle 1 consists of R-CHOP alone; Cycles 2-5 include R-CHOP on Day 1 with epcoritamab on Days 1, 8, and 15. In Cycle 2, dexamethasone is administered on epcoritamab treatment days and the following day. In Cycle 6, both R-CHOP and epcoritamab a

Interventions

• DRUG: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone (R-CHOP) — Given orally and intravenously (IV)
• DRUG: Epcoritamab — Given subcutaneously (SC)
• DRUG: Dexamethasone — Given orally
• PROCEDURE: Positron Emission Tomography (PET) — Undergo imaging
• PROCEDURE: Blood specimen collection — Perform Blood work

Primary Outcomes

• Cytokine Release Syndrome (CRS) Rate (Up to day 42)

Secondary Outcomes

• Proportion of Participants with Treatment-emergent Adverse Events (Up to 60 days after treatment)
• Overall Response (OR) (Up to 2 years)
• Duration of Overall Response (Up to 2 years)
• Median Progression-Free Survival (PFS) (Up to 2 years)
• Median Overall Survival (OS) (Up to 2 years.)

Eligibility Criteria

Inclusion Criteria:

1. Participants must have confirmed CD20-positive aggressive B-cell lymphoma, including de novo or transformed diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; primary mediastinal large B-cell lymphoma (PMBCL); T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL); Epstein-Barr virus-positive DLBCL, NOS; or follicular lymphoma grade 3b.
2. Measurable disease per Lugano 2014 criteria.
3. No prior therapy for DLBCL or FL G3B other than corticosteroids or palliative radiotherapy. Of note, a cycle of anthracycline-containing regimen (given as standard of care prior to study enrollment) is allowed, provided that patients will receive a total of six cycles of chemotherapy as part of their treatment plan. Patients who received one cycle of an anthracycline-containing regimen prior to enrollment will proceed directly to Cycle 2 on study.
4. Age ≥18 years
5. Participants must have an International Prognostic Index (IPI) score of 2-5.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
7. Demonstrates adequate organ function as defined below:

   Adequate bone marrow function:

   absolute neutrophil count platelets
   * 1.0 × 10⁹/Litre (L) (with growth factor use allowed)
   * 75 × 10⁹/L

   Exceptions:

   Patients may be enrolled despite not meeting the thresholds above if either of the following applies, provided the Absolute Neutrophil Count (ANC) is ≥0.75 × 10⁹/L:
   1. The patient has received one prior cycle of chemotherapy off study, and cytopenias at Cycle 2, Day 1 of protocol therapy are believed to be due to recent chemotherapy, provided there is evidence of marrow recovery and no other contraindications.
   2. The patient has documented bone marrow involvement by lymphoma, and cytopenias are believed to be disease-related rather than indicative of poor marrow reserve or unrelated pathology. In such cases, enrollment is permitted at the discretion of the investigator if the patient is otherwise eligible and deemed safe to proceed.

   Adequate hepatic function:

   Total bilirubin

   ≤2 × upper limit of normal (ULN) (unless due to Gilbert's)

   Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT)

   ≤3 × institutional upper limit of normal

   Alanine aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT)

   ≤3 × institutional upper limit of normal

   Adequate renal function:

   As assessed by estimated glomerular filtration rate (eGFR)

   Coagulation:

   Prothrombin time (PT) International Normalized Ratio (INR) and Activated partial thromboplastin time aPTT

   ≤1.5 × ULN, unless receiving anticoagulation therapy
8. Left ventricular ejection fraction (LVEF) ≥50% by multigated acquisition (MUGA) or echocardiography at screening.
9. Ability to understand and the willingness to sign a written informed consent document.
10. .Human immunodeficiency virus (HIV)-infected individuals are eligible if the following criteria are met:

    1. Serum HIV viral load is \< lower limit of detection (LLD) and controlled with antiretroviral therapy for at least 1 year prior to enrollment, with confirmatory testing at screening;
    2. CD4 count ≥ 200 cells/microliter (μL) at screening;
    3. Subject is receiving antiretroviral regimens in accordance with current International Acquired Immunodeficiency Syndrome (AIDS) Society guidelines;
    4. No evidence of AIDS-defining illnesses (other than lymphoma diagnosis) or active opportunistic infections;
    5. Antiretroviral therapy does not interfere with study medications.
11. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
12. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
13. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
14. The effects of epcoritamab on the developing human fetus are unknown. For this reason, and because bispecific antibodies may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, or abstinence). Woman with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of epcoritamab or according to the local prescribing information of the standard of care (SOC) regimens, whichever is the longest. Adequate contraception is defined as highly effective methods of contraception. Also refer to the local prescribing information for information regarding c

Trial Locations

• Zuckerberg San Francisco General, San Francisco, California, United States
• University of California, San Francisco, San Francisco, California, United States

Contact Information

• UCSF Hematopoietic Malignancies Clinical Trial Recruitment — CONTACT
  Phone: 877-827-3222
  Email: HDFCCC.Heme@ucsf.edu
• Clinical Trial Recruitment — CONTACT
  Email: cancertrials@ucsf.edu

Study Officials

• Mwanasha Merrill, MD — PRINCIPAL_INVESTIGATOR
  University of California, San Francisco

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