Polatuzumab Vedotin + Rituximab for B-Cell Lymphoma

Overseen By Patrick Reagan

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must not be taking: Investigational drugs

Disqualifiers: CNS lymphoma, Dialysis, HIV, 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: 21 days per cycle

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of medicines, including polatuzumab vedotin (an antibody-drug conjugate), to determine their effectiveness and safety in treating B-cell lymphoma, a type of blood cancer. It specifically targets older adults, aged 75 and up, who have not received standard treatments due to age or health conditions. Suitable candidates are those without extensive prior treatment for this aggressive cancer and who experience symptoms such as frequent fatigue or unexplained weight loss. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that polatuzumab vedotin is usually well-tolerated by patients with non-Hodgkin lymphoma (NHL), but it might not suit those with chronic lymphocytic leukemia (CLL). In cases of diffuse large B-cell lymphoma (DLBCL), it can reduce red or white blood cell counts and increase uric acid levels. Common side effects include tiredness, low blood counts, and nausea.

Rituximab, another part of this treatment, is widely used and generally considered safe, but it can cause side effects like infections and allergic reactions.

Cyclophosphamide and doxorubicin, chemotherapy drugs often used together to treat cancer, can cause side effects such as nausea, hair loss, and a weakened immune system. Prednisone, a steroid, can lead to weight gain, mood changes, and higher blood sugar levels.

Overall, studies have examined the safety of combining these treatments, and each has known side effects that doctors monitor closely during treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Polatuzumab Vedotin for B-cell lymphoma because it offers a new approach by specifically targeting cancerous B-cells. Most current treatments, like the R-CHOP regimen, attack both cancerous and healthy cells, leading to more side effects. Polatuzumab Vedotin is an antibody-drug conjugate, which means it combines an antibody that specifically seeks out B-cells with a potent chemotherapy drug. This targeted action allows it to deliver the chemotherapy directly to the cancer cells, potentially improving effectiveness and reducing damage to healthy cells. This focused strategy may lead to better outcomes and fewer side effects for patients.

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

Research has shown that polatuzumab vedotin, a treatment in this trial, can improve effectiveness and survival rates in patients with advanced diffuse large B-cell lymphoma (DLBCL). Several studies have reported encouraging results for patients receiving polatuzumab vedotin, with many achieving complete responses and experiencing longer periods without disease progression. Rituximab, another component of the treatment in this trial, enhances treatment success and long-term outcomes in aggressive lymphomas like DLBCL. The combination of these two drugs, along with others, targets and destroys cancerous B-cells, potentially leading to better outcomes for patients with this type of lymphoma. Overall, existing evidence supports the potential benefits of these treatments in managing DLBCL. ^{6 7 8 9 10}

Who Is on the Research Team?

Patrick Reagan

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for men and women aged 75 or older with DLBCL, including those who've had certain prior treatments for indolent lymphoma but not an anthracycline regimen. They must have adequate organ function, no serious medical issues that could affect the study, and agree to contraception if applicable.

Inclusion Criteria

I have received one cycle of a specific chemotherapy for my aggressive disease.

I am not suitable for standard R-CHOP treatment due to my age or health conditions.

Ejection fraction of ≥ 45% on echocardiogram or MUGA

Exclusion Criteria

I have completed treatment for my stage 1 cancer.

I had another cancer but have been in remission for over 3 years without treatment.

I am currently on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive polatuzumab vedotin in combination with R-miniCHP for 21 days per cycle

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Polatuzumab vedotin
• Prednisone
• Rituximab

Trial Overview The effectiveness and safety of polatuzumab vedotin combined with R-miniCHP (rituximab, cyclophosphamide, doxorubicin hydrochloride hydrate [doxorubicin], prednisone) are being tested in patients over 75 years old with diffuse large B-cell lymphoma (DLBCL).

How Is the Trial Designed?

Group I: Experimental: Polatuzumab Vedotin and R-CHOP Experimental Treatment 5 Interventions

The dose of polatuzumab vedotin for each patient will be 1.8 mg/kg (IV for 21 days)

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?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Rituximab enhances the effectiveness of the anti-CD19 immunotoxin BU12-SAPORIN in treating human lymphoma cells, leading to complete inhibition of cell proliferation and increased apoptosis in vitro.

In a mouse model, the combination of rituximab and BU12-SAPORIN showed significantly better therapeutic outcomes than either treatment alone, suggesting a strong potential for this combination therapy in lymphoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-CD20 antibody rituximab augments the immunospecific therapeutic effectiveness of an anti-CD19 immunotoxin directed against human B-cell lymphoma. Flavell, DJ., Warnes, SL., Bryson, CJ., et al.[2018]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

The study compares two types of immunotoxins, HMW-IT and LMW-IT, which combine Rituximab with the toxin saporin-S6, showing that HMW-IT has a stronger anti-tumor effect against CD20+ lymphoma cells due to its higher toxin payload.

HMW-IT's enhanced efficacy suggests it could improve lymphoma therapy, especially for patients who do not respond to standard treatments, by effectively targeting antigens that are less likely to be internalized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin. Bortolotti, M., Bolognesi, A., Battelli, MG., et al.[2019]

90Y-ibritumomab tiuxetan, a radioimmunoconjugate targeting CD20, demonstrated an overall response rate (ORR) of 80% in relapsed non-Hodgkin's lymphoma patients, significantly higher than the 44% ORR seen with rituximab alone.

In patients with low-grade non-Hodgkin's lymphoma, the response rate was even more impressive at 82%, indicating that 90Y-ibritumomab tiuxetan may be a more effective treatment option for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ibritumomab tiuxetan radioimmunotherapy for patients with relapsed B-cell non-Hodgkin's lymphoma. Witzig, TE.[2016]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., 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]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[2023]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

The study evaluated the antibody-drug conjugate polatuzumab vedotin (pola) combined with rituximab/obinutuzumab and chemotherapy in treating B-cell non-Hodgkin lymphoma, showing that pola's pharmacokinetics were consistent and dose-proportional across different treatment cycles.

There were no significant drug-drug interactions between pola and the chemotherapy regimen (R/G-CHP), indicating that pola can be safely used in combination with these treatments for previously untreated diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Shemesh, CS., Agarwal, P., Lu, T., et al.[2020]

In a study of seven patients with non-Hodgkin lymphoma treated with rituximab (RTX) and chemotherapy, there was a significant reduction in their ability to mount an immune response to vaccines, indicating increased susceptibility to infections.

The introduction of intravenous immunoglobulin (IVIg) therapy was crucial for managing recurrent infections, such as pneumonia and sinusitis, highlighting the importance of monitoring and addressing hypogammaglobulinemia in patients undergoing RTX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. de Souza, KJ., Ferro, RS., Prestes-Carneiro, LE., et al.[2019]

In a study of 71 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) showed an overall response rate of 47.9%, with a complete response rate of 32.4% after a median of 3 treatment cycles.

The treatment demonstrated a manageable safety profile, with the most common severe side effects being grade 3-4 neutropenia and thrombocytopenia, indicating that Pola-BR is a promising and effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey. Dal, MS., Ulu, BU., Uzay, A., et al.[2023]

In a study of 74 elderly patients with diffuse large B-cell lymphoma, both R-THP-COP and R-CHOP regimens showed similar overall response rates (around 94.6%) and comparable 2-year survival rates, indicating that R-THP-COP is an effective alternative to R-CHOP.

Both treatment regimens had high rates of neutropenia as a common side effect, but neither regimen significantly impaired cardiac function, suggesting that R-THP-COP is a safe option for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3A Comparison between R-THP-COP and R-CHOP Regimens for the Treatment of Diffuse Large B-cell Lymphoma in Old Patients: A Single-institution Analysis. Araie, H., Sakamaki, I., Matsuda, Y., et al.[2018]

Citations

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ABCL-529: Real-World Outcomes With Polatuzumab ... Despite a small sample size and high data censorship, outcomes suggest feasibility and potential benefit. Challenges include drug access, treatment continuity, ...

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ABCL-529: Real-World Outcomes With Polatuzumab ... Despite a small sample size and high data censorship, outcomes suggest feasibility and potential benefit. Challenges include drug access, treatment continuity, ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/07853890.2025.2566871

First-line treatment with polatuzumab vedotin improves ... First-line treatment with polatuzumab vedotin improves efficacy and survival in newly diagnosed patients with advanced diffuse large B-cell lymphoma: a ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-00992?af=R

Efficacy and Safety of Glofitamab Plus Polatuzumab ... Efficacy and Safety of Glofitamab Plus Polatuzumab Vedotin in Relapsed/Refractory Large B-Cell Lymphoma Including High-Grade B-Cell Lymphoma: ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25925619/

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Safety and activity of the anti-CD79B antibody–drug ... Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further ...

8. polivy.com polivy.com/newly-diagnosed/rchp.html

POLIVY® (polatuzumab vedotin-piiq) for certain types of ... POLIVY may lower your red or white blood cell counts and increase uric acid levels. The most common side effects of POLIVY when used in DLBCL after at least 2 ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2115304

Polatuzumab Vedotin in Previously Untreated Diffuse ... Polatuzumab vedotin is an antibody–drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.

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Roche | Polivy (polatuzumab vedotin) Polivy is the first approved therapy in nearly 20 years for the first-line treatment of diffuse large B-cell lymphoma (DLBCL). Polivy is currently approved ...