Epcoritamab + Rituximab-mini CVP for Lymphoma

Overseen By Dai Chihara, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS lymphoma, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24-48 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a new drug, epcoritamab, to the existing treatment for diffuse large B-cell lymphoma (DLBCL) can better control the disease. Researchers aim to determine if this combination is safe and effective. Individuals newly diagnosed with certain aggressive lymphomas, who have not received prior treatment, might be suitable candidates, particularly if they cannot undergo strong chemotherapy. The trial involves receiving a series of medications, including an injection of epcoritamab, over several treatment cycles. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressant therapy or chronic corticosteroids at a dose higher than 10 mg/day of prednisone, you may need to adjust your medication as these are excluded within 28 days of the first dose of the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that epcoritamab can cause some side effects, but many are manageable. In studies, 51% of patients with large B-cell lymphoma (LBCL) experienced cytokine release syndrome (CRS), a condition where the body releases too many proteins called cytokines. Most cases were mild, with 37% being grade 1 and 17% being grade 2, while only 2.5% were more serious grade 3 cases. Many people tolerate the treatment well, though some reported injection site reactions, fatigue, and common colds.

The other drugs in the R-miniCVP regimen—rituximab, cyclophosphamide, vincristine, and prednisone—are well-known and have been used for a long time to treat various types of cancer. Their side effects are well-documented and usually include nausea, fatigue, and possible hair loss. Because these drugs have been used frequently, doctors know how to manage their side effects effectively.

Overall, while epcoritamab and the R-miniCVP regimen have their risks, past patients have demonstrated that these treatments can be handled safely with proper care and monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lymphoma, which often involve chemotherapy and monoclonal antibodies like rituximab, the combination of Epcoritamab with R-miniCVP offers a novel approach. Epcoritamab is a bispecific antibody designed to engage both T-cells and cancer cells, effectively directing the immune system to target and destroy lymphoma cells more efficiently. Researchers are excited about Epcoritamab because it is administered subcutaneously, allowing for potentially improved patient comfort and compliance compared to traditional intravenous therapies. This dual-targeting mechanism and convenient delivery method set it apart from existing options, bringing hope for more effective and patient-friendly lymphoma treatments.

What evidence suggests that this trial's treatments could be effective for DLBCL?

Research has shown that epcoritamab holds promise for treating aggressive B-cell lymphoma. One study found that 64.3% of patients responded well to the treatment, with 47.6% achieving complete remission, meaning no detectable cancer. Another study reported a 63.1% overall response rate, with 40.1% of patients reaching complete remission. These findings suggest that epcoritamab can effectively target and reduce lymphoma cells. In this trial, participants will receive a combination of epcoritamab with R-miniCVP, which may improve outcomes for patients newly diagnosed with DLBCL (Diffuse Large B-Cell Lymphoma). ^{6 7 8 9 10}

Who Is on the Research Team?

Dai Chihara, M D

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed Diffuse Large B-cell Lymphoma who are unfit or ineligible for certain chemotherapy due to age, heart function, previous treatments, or other health issues. Participants must have adequate organ and marrow function, not be pregnant or breastfeeding, agree to contraception if of childbearing potential, and cannot have HIV/Hepatitis B/C infections or severe allergies to similar drugs.

Inclusion Criteria

I cannot receive anthracycline-based chemotherapy due to specific health reasons.

Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.

Ejection fraction (EF) <50% but ≥30%

Exclusion Criteria

My skin cancer was treated successfully and shows no signs of returning.

I have lymphoma in my brain or spinal cord.

I do not have uncontrolled HIV, Hepatitis B or C, or any significant active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive R-miniCVP for up to 6 cycles and epcoritamab starting from Cycle 2 for up to 11 cycles

24-48 weeks

Weekly visits for injections during each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Epcoritamab
• Prednisone
• Rituximab
• Vincristine

Trial Overview

The study tests whether adding Epcoritamab to the R-miniCVP treatment (Rituximab combined with Cyclophosphamide, Vincristine, Prednisone) is effective in controlling DLBCL. It also examines the safety of this drug combination in patients who meet specific health criteria.

How Is the Trial Designed?

Group I: R-miniCVP+ Epcoritamab Experimental Treatment 5 Interventions

Starting on Day 1 of Cycle 2, you will also receive epcoritamab 1 time each week (Days 1, 8, 15, and 22 of each cycle). Epcoritamab is given as an injection under your skin, after you complete your dose of R-miniCVP. You may receive up to 6 cycles of R-miniCVP (Cycles 1-6) and up to 11 cycles of epcoritamab (Cycles 2-12), depending on how the disease responds to treatment.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 321 patients with untreated follicular lymphoma, adding rituximab to the standard CVP treatment significantly improved long-term outcomes, including time to treatment failure and overall survival, with a 4-year survival rate of 83% for R-CVP compared to 77% for CVP alone.

The addition of rituximab also enhanced response rates and time to progression, demonstrating its effectiveness across various prognostic subgroups, while the Follicular Lymphoma International Prognostic Index remained a strong predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. Marcus, R., Imrie, K., Solal-Celigny, P., et al.[2022]

Rituximab has revolutionized lymphoma treatment, showing effectiveness as a single agent in all types of B-cell lymphomas, both indolent and aggressive.

Combining rituximab with chemotherapy (like CHOP) significantly improves treatment outcomes for large-cell lymphomas without adding significant toxicity, establishing it as the standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and chemotherapy for aggressive lymphomas: a significant advance in therapy. Hagemeister, FB.[2015]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

The addition of rituximab to the CVP chemotherapy regimen significantly improved overall response rates in previously untreated patients with advanced follicular lymphoma, achieving 81% overall response compared to 57% with CVP alone.

Patients receiving the R-CVP combination experienced a much longer time to disease progression (32 months) and time to treatment failure (27 months) compared to those on CVP alone (15 months and 7 months, respectively), without increasing treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Marcus, R., Imrie, K., Belch, A., et al.[2022]

In a phase 3 study involving 447 treatment-naive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma, bendamustine plus rituximab (BR) was found to be noninferior to standard rituximab-chemotherapy regimens (R-CHOP/R-CVP) in achieving complete response rates (31% vs 25%).

While BR showed a higher overall response rate (97% vs 91%), it also had a higher incidence of vomiting and drug-hypersensitivity reactions compared to standard therapies, indicating a need to consider safety profiles when choosing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Flinn, IW., van der Jagt, R., Kahl, BS., et al.[2022]

In a study of 250 patients with indolent non-Hodgkin lymphomas, both R-CVP and R-CHOP regimens followed by rituximab maintenance showed similar efficacy in terms of event-free survival and progression-free survival after a median follow-up of over 5 years.

R-CVP demonstrated significantly lower rates of severe adverse events compared to R-CHOP, making it a safer option for induction treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. Walewski, J., Paszkiewicz-Kozik, E., Michalski, W., et al.[2020]

Rituximab, an anti-CD20 monoclonal antibody, significantly improves tumor remission and patient survival when used in combination with chemotherapy for patients with B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), based on phase III trials.

The drug is generally well tolerated and has been shown to prolong remission when used as maintenance therapy, making it a valuable treatment option included in current guidelines for advanced-stage B-cell NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Cvetković, RS., Perry, CM.[2018]

In a phase II trial involving 40 patients with CD20+, B-cell non-Hodgkin's lymphoma, the R-CHOP combination therapy resulted in a remarkable overall response rate of 100%, with 87% of patients achieving a complete or unconfirmed complete response.

The median time to disease progression (TTP) was 82.3 months and the duration of response (DR) was 83.5 months, indicating that R-CHOP therapy provides a long-lasting effect for patients with relapsed or newly diagnosed indolent non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. Czuczman, MS., Weaver, R., Alkuzweny, B., et al.[2015]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

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