ViPOR-P for B-Cell Lymphoma

Overseen By Christopher J Melani, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Active CNS lymphoma, HIV, Pregnancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 18 weeks

55 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Aggressive B-cell lymphomas can be cured but people with disease that resists treatment or that returns after treatment have poor outcomes with standard therapies. Indolent B-cell lymphomas are generally incurable with standard therapy and treatment is aimed at controlling symptoms and achieving a durable remissions. Researchers want to see if a combination of drugs can help patients with both aggressive and indolent B-cell lymphomas. Objective: To learn if it is safe and effective to give polatuzumab along with venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide to people with certain B-cell lymphomas. Eligibility: Adults ages 18 and older with relapsed and/or refractory B-cell lymphoma who have had at least one prior cancer treatment. Design: Participants will be screened with: Medical history Physical exam Assessment of how they do their daily activities Blood and urine tests Heart function test Tissue biopsy (if needed) Body imaging scans (may get a contrast agent through an intravenous (IV) catheter) Participants will have a bone marrow aspiration and/or biopsy. A needle will be put into the hipbone. Bone marrow will be removed. Participants may give blood, tissue, saliva, or cheek swab samples. They may have optional biopsies. Screening tests will be repeated during the study. Treatment will be given for up to 6 cycles. Each cycle lasts 21 days. Participants will take venetoclax and prednisone tablets by mouth. They will take ibrutinib and lenalidomide capsules by mouth. They will get obinutuzumab and polatuzumab by IV infusion. They will keep a medicine diary. Participants will visit the clinic 30 days after treatment ends. They will have follow-up visits for 5 years. If needed, they can visit their local doctor instead. They may be contacted by phone, mail, etc., for the rest of their life....

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude participants who need to use warfarin or certain other medications due to potential interactions. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the ViPOR-P drug for B-Cell Lymphoma?

The combination of ibrutinib and venetoclax has shown improved outcomes in chronic lymphocytic leukemia, and polatuzumab vedotin has demonstrated activity in diffuse large B-cell lymphoma. Additionally, the combination of ibrutinib, obinutuzumab, and venetoclax has provided high response rates in mantle cell lymphoma, suggesting potential effectiveness for B-Cell Lymphoma. ^{1 2 3 4 5}

Is the ViPOR-P treatment generally safe for humans?

Polatuzumab vedotin, a component of the ViPOR-P treatment, has been studied in various clinical trials and is generally considered safe when used in combination with other drugs for B-cell lymphoma. It has a low incidence of anti-drug antibodies, which suggests a low risk of immune reactions. Additionally, the combination of ibrutinib, obinutuzumab, and venetoclax has been well tolerated in patients with mantle cell lymphoma, showing high response rates. ^{2 5 6 7 8}

What makes the ViPOR-P drug unique for treating B-cell lymphoma?

The ViPOR-P drug is unique because it combines multiple agents, including polatuzumab vedotin, which is a first-in-class antibody-drug conjugate targeting CD79b on B cells, with other drugs like ibrutinib and venetoclax that target different pathways in cancer cells, potentially offering a more comprehensive approach to treating B-cell lymphoma compared to standard treatments. ^{4 9 10 11 12}

Research Team

Christopher J Melani, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with B-cell lymphoma that has come back or didn't respond to treatment can join. They must have tried at least one cancer therapy, be in good health otherwise, and agree to use birth control. People with certain types of lymphoma like MCL or active CNS involvement, pregnant women, those with liver disease or HIV, and anyone on conflicting medications are excluded.

Inclusion Criteria

My lymphoma is an aggressive type, such as DLBCL or Burkitt.

My B-cell lymphoma didn't respond or came back after treatment with an anti-CD20 drug.

My aggressive B-cell lymphoma didn't respond to or came back after treatment with an anthracycline.

Exclusion Criteria

Evidence of active tumor lysis syndrome

You are allergic to xanthine oxidase inhibitors and rasburicase or any of the study drugs.

I do not have any unmanaged ongoing illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for assessments and tests

Treatment

Participants receive a combination of venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide, and polatuzumab over 6 cycles, each lasting 21 days

18 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for 5 years

5 years

Follow-up visits every 3-6 months

Treatment Details

Interventions

• Ibrutinib
• Obinutuzumab
• Polatuzumab
• Prednisone
• Revlimid
• Venetoclax

Trial Overview The trial tests a drug combo (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Revlimid & Polatuzumab) for B-cell lymphomas resistant to standard treatments. Participants will take some drugs orally and receive others through IV for up to six cycles lasting 21 days each.

Participant Groups

Group I: Arm 2: Dose Expansion Experimental Treatment 6 Interventions

Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles)

Group II: Arm 1: Dose Escalation Experimental Treatment 6 Interventions

Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax

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

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.

Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. Wanner, D., Steurer, M.[2020]

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]

In a phase 3 trial with 523 patients, the combination of ibrutinib and venetoclax significantly improved progression-free survival compared to the traditional FCR treatment, with only 12 patients experiencing disease progression or death in the ibrutinib-venetoclax group versus 75 in the FCR group.

The study also found that 65.9% of patients on ibrutinib-venetoclax achieved undetectable measurable residual disease (MRD) in bone marrow after 5 years, indicating effective disease control, although there was a higher incidence of serious cardiac adverse events in this group compared to FCR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. Munir, T., Cairns, DA., Bloor, A., et al.[2023]

Polatuzumab vedotin (PV) is an innovative antibody-drug conjugate that has been approved by the US FDA for treating refractory/relapsed diffuse large B-cell lymphoma, particularly in patients who are not eligible for stem cell transplants.

In a pivotal Phase II trial, PV demonstrated significant efficacy and an acceptable safety profile when used in combination with bendamustine and rituximab, highlighting its potential as a valuable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. Camus, V., Tilly, H.[2021]

The combination of venetoclax, ibrutinib, and obinutuzumab is well tolerated in patients with relapsed and untreated mantle cell lymphoma (MCL), with no dose-limiting toxicities reported and a maximum tolerated dose of 400 mg per day established for venetoclax.

High response rates were observed, with a complete response rate of 67% in relapsed patients and 86.6% in untreated patients, along with significant minimal residual disease clearance in 71.5% of relapsed and 100% of untreated patients after three cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Le Gouill, S., Morschhauser, F., Chiron, D., et al.[2021]

In a study of 57 patients with relapsed large B-cell lymphoma after CAR T-cell therapy, polatuzumab vedotin (PV) showed a response rate of 44%, with 14% achieving complete remission, indicating its potential efficacy in this challenging patient population.

The median progression-free survival was only 10 weeks, and factors like bone marrow involvement and high lactate dehydrogenase levels were linked to shorter survival, highlighting the need for further research on treatment resistance and consolidation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. Gouni, S., Rosenthal, AC., Crombie, JL., et al.[2023]

Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells, delivering a cytotoxic agent (MMAE) to inhibit cell division and induce cell death, making it a promising treatment for certain blood cancers.

In June 2019, polatuzumab vedotin received accelerated FDA approval for use with bendamustine and rituximab in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and it is currently under review in the EU and in various stages of development for other related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: First Global Approval. Deeks, ED.[2023]

Polatuzumab vedotin (POLIVY®) is an effective treatment for adult patients with diffuse large B-cell lymphoma, approved after showing significant anti-cancer activity by delivering a potent drug directly to B cells.

The incidence of anti-drug antibodies (ADA) against polatuzumab vedotin is low, likely due to its mechanism of action that targets and kills B cells, which minimizes immune response and supports a favorable benefit/risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Dere, RC., Beardsley, RL., Lu, D., et al.[2023]

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]

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]

Polatuzumab vedotin, an antibody-drug conjugate, demonstrated an acceptable safety profile in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), with a recommended phase 2 dose of 2.4 mg/kg showing objective responses in 23 out of 42 evaluable patients.

In contrast, the treatment was not effective for patients with chronic lymphocytic leukaemia (CLL), as no objective responses were observed, highlighting the need for further assessment of polatuzumab vedotin specifically in NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Palanca-Wessels, MC., Czuczman, M., Salles, G., et al.[2018]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

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

Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. [2021]

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

Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. [2021]

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

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: First Global Approval. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. [2023]

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

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

11. 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]

12. England pubmed.ncbi.nlm.nih.gov

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. [2018]