Polatuzumab Vedotin + Combination Chemotherapy for Lymphoma

Not currently recruiting at 2 trial locations

Overseen By Dipenkumar Modi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Barbara Ann Karmanos Cancer Institute

Must not be taking: Anthracyclines, Anti CD 20 antibodies

Disqualifiers: CNS lymphoma, HIV, Hepatitis B, 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: 9

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for certain types of untreated lymphoma, including double or triple hit lymphoma and high-grade B-cell lymphoma. It combines polatuzumab vedotin (Polivy) with chemotherapy to determine if this mix is more effective than chemotherapy alone. Polatuzumab vedotin targets cancer cells directly to inhibit their growth. The trial seeks participants who have not yet received treatment for their lymphoma and have a confirmed diagnosis of these specific types. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, it mentions that you should not have received certain cancer treatments before starting the trial, except for one prior cycle of a specific chemotherapy regimen. It's best to discuss your current 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 a treatment combining polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) may be effective for certain types of lymphoma. Patients generally tolerated this treatment well in studies.

Specifically, the POLARIX study found that patients with diffuse large B-cell lymphoma (DLBCL) who received Pola-R-CHP experienced longer periods without disease progression. While some side effects occurred, most were manageable. Common issues included low blood cell counts, tiredness, and nausea, but serious side effects were rare.

These studies suggest that the treatment is relatively safe for patients, with benefits often outweighing the risks. However, discussing any concerns with a healthcare professional before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for lymphoma?

Researchers are excited about the treatment combining polatuzumab vedotin with R-CHP (rituximab, cyclophosphamide, doxorubicin hydrochloride, and prednisolone/prednisone) for lymphoma because it introduces a novel mechanism of action. Unlike standard treatments that typically rely on chemotherapy alone, polatuzumab vedotin is an antibody-drug conjugate that specifically targets and binds to the CD79b protein on B-cells, delivering a toxic payload directly to cancer cells. This targeted approach aims to increase the precision of the treatment, potentially reducing harm to healthy cells and improving outcomes compared to traditional regimens. Additionally, the combination with R-CHP leverages proven chemotherapy agents, which may enhance the overall effectiveness of the therapy.

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

Research shows that a treatment combining polatuzumab vedotin with R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone), which participants in this trial will receive, holds promise for treating certain aggressive lymphomas. Studies have found that this combination helps patients live longer without their disease worsening. Specifically, for diffuse large B-cell lymphoma (DLBCL), this new combination controls the disease better than the standard R-CHOP treatment. It targets cancer cells and delivers a potent drug directly to them, potentially increasing the treatment's effectiveness. While polatuzumab vedotin is already approved for some uses, this trial explores its potential benefits for more specific types of aggressive lymphoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Dipenkumar Modi, M.D.

Principal Investigator

Barbara Ann Karmanos Institute

Are You a Good Fit for This Trial?

This trial is for patients with previously untreated high-grade B-cell lymphoma, including double or triple hit and double expressor subtypes. Participants must have a measurable lesion, normal heart function (LVEF >= 45%), adequate blood counts, and agree to use effective contraception if of childbearing potential. They should be able to follow the study protocol and have a life expectancy of at least 24 weeks.

Inclusion Criteria

You have a certain type of high-grade B-cell lymphoma called HGBL NOS subtype.

Ability and willingness to comply with the study protocol procedures

Left ventricular ejection fraction (LVEF) >= 45% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

Exclusion Criteria

You cannot participate if you have had a severe allergic reaction to any of the drugs in the treatment plan or have an allergy to ingredients used to make the drugs.

You have had other types of cancer that could make it harder to follow the rules of this study or understand the results. There are some exceptions, but not all types of cancer are allowed.

You have not received any treatment for cancer with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy or experimental drugs before starting the clinical trial, except for some specific cases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive polatuzumab vedotin and combination chemotherapy (R-CHP) every 21 days for up to 6 cycles

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Polatuzumab Vedotin
• Prednisolone
• Prednisone
• Rituximab

Trial Overview The trial is testing polatuzumab vedotin combined with chemotherapy drugs like rituximab, cyclophosphamide, doxorubicin hydrochloride, and prednisone against lymphoma. The goal is to see if this combination works better than standard chemotherapy alone in treating aggressive forms of B-cell lymphoma.

How Is the Trial Designed?

Group I: Treatment (polatuzumab vedotin, R-CHP) Experimental Treatment 7 Interventions

Patients receive prednisone PO, prednisolone IV, or methylprednisolone IV on days 1-5. Patients also receive rituximab IV, polatuzumab vedotin IV over 30-90 minutes, cyclophosphamide IV, and doxorubicin hydrochloride IV on day 1. 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?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

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]

In a study of 21 patients with advanced non-Hodgkin's lymphoma treated with the VINAP chemotherapy regimen, 76% showed a response, with 23% achieving complete remission, indicating significant efficacy for this heavily pretreated group.

The VINAP regimen had an acceptable safety profile, with manageable side effects like myelosuppression and mucositis, but no severe neurological issues or skin reactions were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vindesine, CCNU, high-dosage ara-C, and prednisolone (VINAP regimen) in the treatment of relapsing or refractory non-Hodgkin's lymphomas]. Domingo Albós, A., Callís, M., Juliá, A., et al.[2013]

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 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]

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 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]

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 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 81 patients with advanced diffuse large cell lymphoma, the epipodophyllotoxin VP-16-213 alone achieved a complete remission rate of 55%, while its combination with doxorubicin also showed a high remission rate of 62%, indicating that VP-16-213 is an effective treatment option.

The combination of VP-16-213 with cyclophosphamide was found to be inferior, with a complete remission rate of only 29%, suggesting that this combination may not be beneficial for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP-16-213 in the treatment of stage III and IV diffuse large cell lymphoma. Jacobs, P., King, HS., Dent, DM., et al.[2019]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

In a study of 19 HIV patients undergoing chemotherapy for non-Hodgkin's lymphoma, HAART did not significantly alter the pharmacokinetics of doxorubicin (DOX), suggesting that the way the body processes DOX remains consistent regardless of HAART treatment.

However, the area under the concentration curve (AUC) of DOX was linked to higher levels of hematologic toxicity in patients receiving CHOP alone, indicating that other factors may contribute to increased toxicity when HAART is also administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma. Toffoli, G., Corona, G., Cattarossi, G., et al.[2020]

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]

Polatuzumab vedotin, when combined with bendamustine and rituximab (polatuzumab-BR), is an effective treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), offering a new therapeutic avenue for those who do not respond to standard treatments.

This combination therapy is considered safe and is particularly beneficial for transplant-ineligible patients, with ongoing trials exploring its use alongside other treatments like CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. Walji, M., Assouline, S.[2021]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39641321/

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab ... Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7061

Efficacy and safety of polatuzumab vedotin plus rituximab ... Background: In the POLARIX study, Pola-R-CHP showed significant improvement in progression free survival (PFS) in previously untreated DLBCL ...

3. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper197938.html

Paper: Five-Year Analysis of the POLARIX Study Pola-R-CHP showed a significant progression-free survival (PFS) benefit vs R-CHOP in patients (pts) with intermediate- or high-risk DLBCL at a median follow-up ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7767/528782/Polatuzumab-Vedotin-Rituximab-Cyclophosphamide

Polatuzumab Vedotin, Rituximab, Cyclophosphamide ... Background: The POLARIX trial demonstrated that Pola-R-CHP provided superior disease control than R-CHOP in previously untreated DLBCL with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03274492

NCT03274492 | A Study Comparing the Efficacy and ... This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP ...

6. link.springer.com link.springer.com/article/10.1007/s00277-025-06619-0

Polatuzumab vedotin, rituximab, cyclophosphamide, ... This study aimed to evaluate the real-world efficacy and safety of Pola-R-CHP in previously untreated DLBCL patients aged ≥ 80 years. In ...