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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the effectiveness and safety of polatuzumab vedotin in combination with R-miniCHP in patients 75 years and older with DLBCL.

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.

What data supports the effectiveness of the drug Polatuzumab Vedotin + Rituximab for B-Cell Lymphoma?

Polatuzumab vedotin, when combined with rituximab and other chemotherapy drugs, has shown effectiveness in treating diffuse large B-cell lymphoma, especially in patients who have not responded to previous treatments. In a study, the combination of polatuzumab vedotin with bendamustine and rituximab resulted in a higher complete response rate compared to bendamustine and rituximab alone, indicating its potential benefit in relapsed or refractory cases. ^{1 2 3 4 5}

Is the combination of Polatuzumab Vedotin and Rituximab safe for treating B-cell lymphoma?

The combination of Rituximab with other chemotherapy drugs like cyclophosphamide and doxorubicin has been shown to be generally safe, with manageable side effects such as neutropenia (low white blood cell count). There were no therapy-related deaths reported in studies involving similar drug combinations. ^{6 7 8 9 10}

What makes the drug Polatuzumab Vedotin + Rituximab unique for treating B-cell lymphoma?

This treatment combines Polatuzumab Vedotin, an antibody-drug conjugate that targets cancer cells, with Rituximab, a monoclonal antibody that enhances the immune system's ability to fight cancer. This combination is unique because it targets the CD79b protein on B-cells, potentially offering a new approach for patients who do not respond well to standard treatments like R-CHOP. ^{6 11 12 13 14}

Research Team

Patrick Reagan

Principal Investigator

University of Rochester

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 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]

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 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 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 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]

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]

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]

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]

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]

References

1. Germany 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. [2023]

2. England 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. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. [2019]

8. United States 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. [2022]

9. Japan 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. [2018]

10. England 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. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin. [2019]

13. England 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. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]