Polatuzumab Vedotin + R-GDP for Diffuse Large B-Cell Lymphoma

Overseen By Leah Randolph

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Infections, Hearing loss, Pregnancy, Cardiac disease, 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: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to treat diffuse large B-cell lymphoma (DLBCL), a type of blood cancer that has returned or did not improve after the first treatment. The study evaluates the effectiveness of adding polatuzumab vedotin, a drug that specifically targets cancer cells, to a standard drug regimen. Participants must have had only one previous treatment for DLBCL and must show evidence of active disease. This trial is open to individuals eligible and ineligible for a stem cell transplant. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior cancer treatment must be completed at least 14 days before starting the trial, so you might need to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that the treatment combination in this study has some safety data from earlier research. The FDA has already approved Polatuzumab vedotin for other uses, indicating its well-known safety profile. Previous studies found it can cause side effects like low blood cell counts and nerve damage, but these effects vary among patients.

Rituximab, part of the standard treatment, is widely used and generally well-tolerated. Common side effects include fever, chills, and infections, but most patients manage these well.

Cisplatin, also part of the standard treatment, can cause side effects like kidney damage, hearing loss, and nausea. However, these are monitored and managed during treatment.

Gemcitabine may cause side effects like low blood counts and nausea, but these are usually manageable with medical support.

Dexamethasone is a steroid that helps reduce inflammation and manage side effects. It may cause mood swings and increased appetite.

Overall, while each part of this treatment can have side effects, they are generally manageable with proper medical care. Past research has shown these drugs can be safe for many patients, but individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Polatuzumab Vedotin with R-GDP for treating diffuse large B-cell lymphoma because it offers a fresh approach compared to current therapies like R-CHOP. Polatuzumab Vedotin is an antibody-drug conjugate that specifically targets cancer cells and delivers a potent chemotherapy agent directly to them, minimizing damage to healthy cells. This targeted mechanism is different from traditional chemotherapy, which affects both cancerous and healthy cells. By combining this with existing drugs like Rituximab and Gemcitabine, the treatment has the potential to be more effective and reduce side effects, offering new hope for patients whose cancer has returned or resisted initial treatments.

What evidence suggests that this treatment might be an effective treatment for diffuse large B-cell lymphoma?

Research has shown that adding polatuzumab vedotin (PV) to the standard R-GDP treatment (which includes rituximab, gemcitabine, dexamethasone, and cisplatin) can improve outcomes for people with relapsed or hard-to-treat diffuse large B-cell lymphoma (rrDLBCL). Polatuzumab vedotin is a drug that targets a protein called CD79b, commonly found on these cancer cells. This targeting helps deliver chemotherapy directly to the cancer cells, enhancing its effectiveness. In this trial, participants will receive the combination of PV with R-GDP. Patients who received PV in similar situations showed better response rates compared to those who only received standard treatments. This suggests that combining PV with R-GDP might be a promising option for those whose lymphoma has returned or did not respond to initial treatments. ^{4 6 7 8 9}

Who Is on the Research Team?

Christopher E. Dittus

Principal Investigator

Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with diffuse large B-cell lymphoma that has returned after one prior treatment. They can be eligible or ineligible for a stem cell transplant, must have an ECOG Performance Status of 0-2, and show active disease on scans. Exclusions include severe allergies to monoclonal antibodies, significant heart or lung issues, hearing loss affecting daily life, pregnancy/breastfeeding intentions within a year post-treatment, and previous polatuzumab vedotin exposure.

Inclusion Criteria

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information

I can take care of myself and am up and about more than half of my waking hours.

I finished my last cancer treatment at least 14 days ago and have recovered from its side effects.

Exclusion Criteria

I do not have any severe infections that could increase my risk during the study.

History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine

I have been treated with polatuzumab vedotin before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the PV-RGDP chemotherapy regimen for relapsed or refractory diffuse large B-cell lymphoma

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Dexamethasone
• Gemcitabine
• Polatuzumab Vedotin (PV)
• Rituximab

Trial Overview

The study tests the effectiveness of adding polatuzumab vedotin (PV) to the standard rrDLBCL salvage therapy regimen (rituximab-gemcitabine-dexamethasone-cisplatin). PV-RGDP aims to improve response rates in patients whose cancer returned after initial treatment. The combination isn't FDA-approved yet; this trial will assess its efficacy.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 7 Interventions

The subjects with diffuse large B-cell lymphoma were relapsed or refractory after the first treatment and receiving the study protocol treatment.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

The recommended phase II dose (RP2D) of pinatuzumab vedotin for treating relapsed/refractory non-Hodgkin lymphoma was established at 2.4 mg/kg, which was well tolerated with manageable side effects, primarily neutropenia and peripheral neuropathy.

At the RP2D, pinatuzumab vedotin showed promising antitumor activity, with objective responses in 36% of patients with diffuse large B-cell lymphoma and 50% of patients with indolent non-Hodgkin lymphoma, while no responses were observed in chronic lymphocytic leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Anti-CD22 Antibody-Drug Conjugate Pinatuzumab Vedotin with/without Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma. Advani, RH., Lebovic, D., Chen, A., et al.[2018]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79B, is effective for treating relapsed/refractory diffuse large B-cell lymphoma when combined with bendamustine and rituximab.

Research by Kawasaki et al. suggests potential mechanisms of resistance to polatuzumab vedotin in lymphoma cells, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. Tarantelli, C., Bertoni, F.[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 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 shown significant clinical efficacy in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and received accelerated FDA approval for use in patients who have failed at least two prior therapies.

The drug is currently being evaluated in combination with other therapies for previously untreated DLBCL patients, indicating its potential to play a broader role in the treatment of this heterogeneous disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma. Assi, R., Masri, N., Dalle, IA., et al.[2021]

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]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

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]

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]

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