Polatuzumab Vedotin + Chemotherapy for Large B-Cell Lymphoma

Overseen By Ryan Lynch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must not be taking: Monoclonal antibodies, Investigational therapy

Disqualifiers: Burkitt lymphoma, Organ transplant, others

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of combining the drug polatuzumab vedotin with chemotherapy for individuals with aggressive large B-cell lymphoma. Polatuzumab vedotin targets specific cancer cells to deliver a cancer-killing agent. The study also examines whether adding another drug, glofitamab, helps stop cancer cell growth. Individuals with untreated aggressive large B-cell lymphoma and severe symptoms may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that prior systemic treatment for lymphoma is not allowed, except for corticosteroids under certain conditions. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that polatuzumab vedotin, when combined with chemotherapy, has promising safety results. In earlier studies, patients with aggressive large B-cell lymphoma received polatuzumab vedotin and experienced manageable side effects. This treatment targets cancer cells directly to destroy them, and patients generally tolerated it well.

When combined with glofitamab, another antibody treatment, the safety profile remained manageable. Studies of this combination in patients with relapsed or difficult-to-treat lymphoma found that side effects were similar to those of other cancer treatments and did not cause severe harm.

Overall, while some side effects can occur, the treatments in this trial have been tested in other studies and are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for large B-cell lymphoma because they incorporate polatuzumab vedotin, a novel antibody-drug conjugate that specifically targets and destroys cancerous B-cells. Unlike traditional chemotherapy alone, which can affect both healthy and cancerous cells, polatuzumab vedotin delivers a powerful anti-cancer agent directly to the malignant cells, potentially increasing effectiveness while minimizing side effects. Additionally, the trial explores the use of glofitamab, a bispecific antibody that recruits immune cells to attack the lymphoma, offering a new mechanism of action not present in standard treatments like R-CHOP. This innovative combination of targeted and immune-mediated therapies could offer new hope for patients with this challenging cancer.

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

Studies have shown that polatuzumab vedotin, one of the treatments in this trial, can help treat aggressive large B-cell lymphoma when combined with other treatments. Research indicates that polatuzumab vedotin alone works in 52% of patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). In this trial, some participants will receive polatuzumab vedotin combined with glofitamab, which has proven even more effective, working in 80% of patients, with 62% achieving a complete response. This combination has demonstrated strong and lasting effects, especially in patients who did not respond well to previous treatments. These findings suggest that polatuzumab vedotin, with or without glofitamab, could effectively treat this type of lymphoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Ryan Lynch, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with untreated aggressive large B-cell lymphoma. Participants must have proper kidney and liver function, no severe allergies to monoclonal antibodies or chemotherapy components, and agree to use effective contraception. Those with prior systemic treatment for lymphoma (except corticosteroids), certain other health conditions, or who are pregnant cannot join.

Inclusion Criteria

Hemoglobin >= 8 g/dL

aPTT within specified limits

ANC >= 1,000/uL

Exclusion Criteria

Pregnancy, lactation, or intent to become pregnant

My CLL/SLL has transformed into a more aggressive form.

I have had cancer before, but it might not affect my eligibility.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive rituximab, polatuzumab vedotin, prednisone, etoposide, doxorubicin, and cyclophosphamide with or without glofitamab for up to 6 cycles

18 weeks

6 cycles, each 21 days apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Periodic visits

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Polatuzumab Vedotin
• Prednisone
• Rituximab

Trial Overview The trial tests polatuzumab vedotin combined with chemotherapy drugs like cyclophosphamide, doxorubicin, etoposide, prednisone, rituximab against aggressive large B-cell lymphoma. Polatuzumab vedotin targets cancer cells specifically to deliver a toxic agent that kills them.

How Is the Trial Designed?

Group I: Arm B (polatuzumab vedotin, glofitamab, chemotherapy) Experimental Treatment 14 Interventions

Patients receive rituximab IV on day 1, polatuzumab vedotin IV on day 1, prednisone PO BID on days 1-5, etoposide IV on days 1-4, doxorubicin IV on days 1-4, and cyclophosphamide IV on day 5. Starting with cycle 2, patients also receive glofitamab, over 4 hours, on day 1 and 8 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan or echocardiography during screening and FDG PET, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.

Group II: Arm A (polatuzumab vedotin, chemotherapy) [CLOSED TO ACCRUAL 05/23/2024] Experimental Treatment 13 Interventions

Patients receive rituximab IV on day 1, polatuzumab vedotin IV on day 1, prednisone PO BID on days 1-5, etoposide IV on days 1-4, doxorubicin IV on days 1-4, and cyclophosphamide IV on day 5. Patients also receive filgrastim SC 24-72 hours after the last dose of each treatment cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan or echocardiography during screening and FDG PET, CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.

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 Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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

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]

A systematic review of 62 randomized controlled trials found that the five-year overall survival rates for ABVD and BEACOPP regimens in advanced-stage Hodgkin lymphoma were 60-97% and 84-99%, respectively, indicating high efficacy for both treatments.

The new treatment A+AVD showed improved efficacy compared to ABVD while maintaining an acceptable tolerability profile, suggesting it may be a more manageable option for patients with advanced-stage Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of front-line treatments for advanced Hodgkin lymphoma: a systematic literature review. Dalal, M., Gupta, J., Price, K., et al.[2021]

This study analyzed over 7.5 million reports from the FDA Adverse Event Reporting System and found that conventional doxorubicin (DOX) has a higher incidence of adverse events compared to liposomal formulations, particularly in terms of myelosuppression and cardiotoxicity.

Liposomal DOX, especially the PEGylated version, showed lower reporting odds ratios for serious side effects like myelosuppression and cardiotoxicity, but a higher risk for palmar-plantar erythrodysesthesia (PPE), indicating the need for careful monitoring when using these formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. Fukuda, A., Tahara, K., Hane, Y., et al.[2022]

The ProMACE-CytoBOM chemotherapy regimen demonstrated a 65% complete remission rate in 78 previously untreated patients with intermediate- and high-grade non-Hodgkin's lymphomas, indicating its efficacy in treating this patient population.

The treatment was found to be feasible and safe, with 84% of the 537 treatment courses administered on schedule and a low rate of fatal toxicities (6%), suggesting it can be effectively implemented in a cooperative group setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study. Miller, TP., Dahlberg, S., Weick, JK., et al.[2017]

In a randomized trial of 118 patients with advanced diffuse lymphocytic lymphoma, the combination of the drug VP-16-213 with doxorubicin resulted in a higher complete remission rate of 54%, compared to 39% with VP-16-213 alone and 26% with VP-16-213 combined with cyclophosphamide.

The study found that combining VP-16-213 with cyclophosphamide led to significantly lower remission rates, suggesting that doxorubicin is a more effective partner for VP-16-213 in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP-16-213 in the treatment of stage III and IV diffuse lymphocytic lymphoma of the large cell (histiocytic) variety: an interim report. Jacobs, P., King, HS., Cassidy, F., et al.[2013]

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 60 previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphomas, the combination chemotherapy regimen CEOP-B/VIMB achieved a high complete remission rate of 77% and a 48-month overall survival rate of 70%.

The treatment demonstrated mild toxicity, making it a favorable option compared to third-generation regimens, while patient outcomes were significantly influenced by factors such as serum LDH levels and performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. De Lena, M., Ditonno, P., Lorusso, V., et al.[2017]

In a multi-institutional study of 69 patients with untreated diffuse large B-cell lymphoma, the DA-EPOCH-R treatment showed high rates of progression-free survival (81%) and overall survival (84%) after a median follow-up of 62 months.

The treatment was well-tolerated, with no significant grade 4 non-hematologic toxicities reported, confirming its safety and efficacy across different subtypes of diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Wilson, WH., Jung, SH., Porcu, P., 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]

Chemotherapy for non-Hodgkin lymphoma in hemodialysis patients requires careful dose adjustments and timing due to the unique pharmacokinetics of drugs and their metabolites, which can lead to either overdose or undertreatment.

An extensive review of 48 studies involving 66 hemodialysis patients undergoing 71 chemotherapy regimens provided valuable insights and recommendations for managing chemotherapy in this population, highlighting the importance of individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for non-Hodgkin lymphoma in the hemodialysis patient: A comprehensive review. Yasuda, H., Yasuda, M., Komatsu, N.[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]

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]

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]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

In a study of 38 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a treatment regimen combining paclitaxel with other drugs resulted in a total response rate of 46%, with 26% achieving a complete response and 20% a partial response.

The regimen demonstrated a manageable safety profile, with major toxicity primarily being hematologic, and only 10% of treatment cycles leading to severe infections, indicating that it is both effective and safe for patients who have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel in combination with mitoxantrone and ifosfamide/mesna for patients with relapsed or refractory non-Hodgkin's lymphoma after failure to cytarabine/cisplatin combination. Romaguera, JE., Rodriguez, MA., Hagemeister, FB., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41115257/

Efficacy and Safety of Glofitamab Plus Polatuzumab ... The median progression-free survival and overall survival (OS) were 12.3 and 33.8 months, respectively (median OS follow-up time, 32.7 months).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... The primary results demonstrated high and durable responses, particularly for patients with primary refractory disease (CR rate, 52.5%) and ...

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

Polatuzumab Vedotin in Previously Untreated Diffuse ... Polatuzumab vedotin has shown efficacy in patients with relapsed or refractory DLBCL, both as a single agent (with an overall response of 52%) ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7782/528262/Effectiveness-and-Safety-of-Polatuzumab-Vedotin

Effectiveness and Safety of Polatuzumab Vedotin-Based ... The 6-month PFS rate was 82.9% in untreated DLBCL patients, which was significantly better than 52.7% in R/R DLBCL patients (p=0.046). The 1- ...

5. roche.com roche.com/media/releases/med-cor-2024-12-08

Five-year results confirm Roche's Polivy combination ... Results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for people with previously untreated DLBCL with the Polivy ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... As of September 2, 2024, 129 patients with LBCL (HGBCL; n = 44, 34.1%), received ≥1 dose of study treatment. The median age was 67 years (range, ...

7. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01530-1/fulltext

ABCL-440 Preliminary Safety and Efficacy Data of Combination ... Polatuzumab vedotin, an antibody drug conjugated to microtubule inhibitor targeting CD79b, demonstrated superior PFS among intermediate- to high-risk DLBCL ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602516/

Clinical Review - Polatuzumab Vedotin (Polivy) - NCBI - NIH The clinical experts reiterated that patients with limited-stage disease experience highly successful outcomes with current R-CHOP approaches and they generally ...