Zanubrutinib + R-CHOP for Diffuse Large B-Cell Lymphoma

Recruiting at 2 trial locations

Overseen By Anna Krivenko

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yazeed Sawalha

Must not be taking: Methotrexate

Disqualifiers: CNS involvement, Cardiovascular conditions, others

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

Compensation: Varies

Number of Visits: 12

Duration: 18 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining zanubrutinib, a Bruton Tyrosine Kinase inhibitor, with R-CHOP, a common treatment mix, can more effectively treat diffuse large B-cell lymphoma (DLBCL). Zanubrutinib blocks a protein called Bruton Tyrosine Kinase, potentially stopping cancer growth. The trial aims to determine the best dose and assess side effects or benefits. Individuals newly diagnosed with DLBCL who haven't undergone extensive prior treatment might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you may need to discuss your current medications with the trial team to ensure they don't interfere with the study treatment.

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

Research has shown that zanubrutinib, when combined with R-CHOP treatment, is generally well-tolerated. Zanubrutinib, a newer medication, is safer than older ones like ibrutinib. One study found that using zanubrutinib with R-CHOP is effective, with manageable side effects for patients with diffuse large B-cell lymphoma (DLBCL). Although all treatments can have side effects, early data suggest this combination is promising in terms of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of zanubrutinib with R-CHOP for treating diffuse large B-cell lymphoma because it introduces a novel mechanism into an established regimen. While standard treatments like R-CHOP target cancer cells through a combination of chemotherapy and monoclonal antibodies, zanubrutinib adds another layer by specifically inhibiting a protein called Bruton's tyrosine kinase (BTK). This targeted approach may enhance the effectiveness of the existing regimen by interfering with pathways that help cancer cells survive and proliferate. The inclusion of zanubrutinib could potentially improve outcomes for patients who do not respond well to current therapies, making this combination a promising advancement in lymphoma treatment.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

This trial will evaluate the addition of zanubrutinib to the R-CHOP treatment for patients with diffuse large B-cell lymphoma (DLBCL). Studies have shown that adding zanubrutinib to R-CHOP may improve patient outcomes compared to R-CHOP alone. Zanubrutinib blocks a protein that aids cancer growth, potentially preventing the cancer from spreading. Previous findings suggest that adding zanubrutinib could extend the time patients live without their cancer worsening. These early results offer promise for those considering this treatment option in the trial. ^{4 5 6 7 8}

Who Is on the Research Team?

Yazeed Sawalha, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with newly diagnosed diffuse large B-cell lymphoma can join this trial if they have a performance status of <=2, meaning they're able to carry out daily activities with some effort. They need normal blood counts and organ function, must not be pregnant or breastfeeding, agree to use contraception, and cannot have other serious health issues that could interfere with the study.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

Ability to understand and sign a written informed consent document and HIPAA consent document

Negative pregnancy test for women of childbearing potential

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

Participation in other interventional clinical trials within 21 days of this trial

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanubrutinib orally once or twice daily on days 1-21, rituximab intravenously on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for up to 6 cycles.

18 weeks

6 cycles, each 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 6 months for 2 years.

24 months

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Prednisone
• Rituximab
• Vincristine Sulfate
• Zanubrutinib

Trial Overview The trial is testing Zanubrutinib combined with R-CHOP chemotherapy regimen for treating patients with DLBCL. It aims to determine the best dose and assess potential benefits or side effects. R-CHOP includes rituximab (immunotherapy), cyclophosphamide, doxorubicin, vincristine (chemotherapies), and prednisone (steroid).

How Is the Trial Designed?

Group I: Treatment (zanubrutinib, R-CHOP) Experimental Treatment 6 Interventions

Patients receive zanubrutinib PO on days 1-21, rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

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?

Yazeed Sawalha

Lead Sponsor

Trials

3

Recruited

60+

Published Research Related to This Trial

In a study of 435 patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP chemotherapy (R-CHOP) was associated with a reduced risk of central nervous system (CNS) relapse, showing a trend of 6.4% risk in R-CHOP patients compared to 9.7% in those treated with CHOP.

Rituximab significantly lowered the risk of CNS relapse (hazard ratio 0.45) and this benefit was even greater for patients who achieved a complete response (hazard ratio 0.18), indicating that R-CHOP is particularly effective in preventing CNS involvement in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Villa, D., Connors, JM., Shenkier, TN., et al.[2022]

In a study of 397 newly diagnosed diffuse large B-cell lymphoma patients treated with R-CHOP, non-neutropenic fever (NNF) occurred in 9.8% of patients, primarily after the third cycle, with interstitial pneumonitis being the most common cause.

NNF was associated with a higher mortality rate of 10.3% compared to febrile neutropenia (FN), which had a mortality rate of only 1.3%, highlighting the need for careful monitoring and management of febrile complications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis. Park, S., Kang, CI., Chung, DR., et al.[2018]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

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 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

In a study of 26 patients with newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL) and extranodal involvement, the combination of zanubrutinib with R-CHOP (ZR-CHOP) demonstrated a high overall response rate of 91.3%, with a complete response rate of 82.6%.

The treatment showed promising safety and efficacy, with a 1-year progression-free survival (PFS) of 80.8% and overall survival (OS) of 88.5%, indicating that ZR-CHOP could be a viable option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement. Geng, H., Jia, S., Zhang, Y., et al.[2023]

The R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard first-line treatment for diffuse large B-cell lymphoma, highlighting its importance in oncology.

Nursing implications of administering R-CHOP are significant, as the combination of these drugs requires careful monitoring for side effects and patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. Sakowski, AK., Patel, PR.[2023]

In a phase III study involving 491 patients with diffuse large B-cell lymphoma, the more intensive treatment regimen DA-EPOCH-R did not show a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) compared to the standard R-CHOP regimen, with 2-year PFS rates of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP.

DA-EPOCH-R was associated with a higher incidence of severe adverse events, including infections and febrile neutropenia, indicating that while it is a more intensive treatment, it does not provide additional survival benefits and carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Bartlett, NL., Wilson, WH., Jung, SH., et al.[2021]

A study involving 86 DLBCL patients identified thirteen specific 5hmC markers in plasma cell-free DNA that are associated with how well patients respond to R-CHOP chemotherapy.

The developed logistic regression model based on these 5hmC modifications showed a prediction performance of 82% sensitivity and 75% specificity, outperforming traditional clinical indicators, suggesting it could be a promising tool for predicting treatment response in a minimally invasive way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients. Chen, HY., Zhang, WL., Zhang, L., et al.[2021]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

In a retrospective study of 11 elderly patients (median age 83) with diffuse large B-cell lymphoma (DLBCL) who were not suitable for standard R-CHOP treatment, 45% achieved a complete response and 27% a partial response to rituximab combined with low-dose trofosfamide.

The treatment showed promising safety with a 1-year overall survival rate of 54.5% and manageable toxicity, primarily leukopenia, suggesting that this combination could be a viable alternative for elderly patients with DLBCL who cannot tolerate more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose trofosfamide plus rituximab is an effective and safe treatment for diffuse large B-cell lymphoma of the elderly: a single center experience. Schelker, RC., Herr, W., Reichle, A., et al.[2019]

In a study of 13 elderly patients (median age 79) with diffuse large B cell lymphoma, the combination of rituximab with CHOP or THP-COP resulted in a 54% complete response rate and a 62% two-year survival rate, indicating its efficacy in this age group.

The treatment was generally safe, although 69% of patients experienced bone marrow suppression, and infusion reactions occurred in 30.7%, which were manageable by adjusting the rituximab dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma]. Kikukawa, M., Miyazaki, K., Kiuchi, A., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11936942/

Zanubrutinib plus R-CHOP improves the treatment effect of ... This retrospective study sought to assess the efficacy and safety of ZR-CHOP in comparison to R-CHOP in treatment-naïve patients with DE-DLBCL.

2. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04418-y

Zanubrutinib, lenalidomide and rituximab plus ... Despite a 5-year progression-free survival (PFS) of approximately 60% in the R-CHOP era (rituximab, cyclophosphamide, doxorubicin, vincristine, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05189197?term=zanubrutinib%20vincristine%20cyclophosphamide%20hydroxydaunorubicin%20prednisone&aggFilters=status:rec%20not%20act%20enr&viewType=Table&rank=5

A Study to Evaluate Efficacy and Safety of Zanubrutinib ... This is a single-arm, open-label Phase II study to evaluate the efficacy and safety of zanubrutinib in combination with Rituximab, cyclophosphamide , ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41136989/

Zanubrutinib, lenalidomide and rituximab plus ... Zanubrutinib, lenalidomide and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as initial treatment in non-germinal ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35697

Zanubrutinib plus R‐CHOP for the treatment of newly ... The patients received zanubrutinib (160 mg by mouth, twice daily) for 6 months and rituximab (375 mg/m2, day 0), cyclophosphamide (750 mg/m2, ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6226/506281/Zanubrutinib-in-Combination-with-Rituximab

Zanubrutinib in Combination with Rituximab ... Although most patients (pts) with DLBCL are cured with R-CHOP, ~40% develop refractory or relapsed disease. Several studies have shown a ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123128230

Zanubrutinib in Combination with Rituximab ... Zanubrutinib, a 2 nd -generation BTK inhibitor with greater selectivity for BTK and improved safety compared with ibrutinib, could be safely combined with R- ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39748728/

Zanubrutinib plus R-CHOP for the treatment of newly ... Zanubrutinib in combination with R-CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for ...