VIPOR Regimen for CNS-involved B-Cell Lymphoma

Overseen By NCI Medical Oncology Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: BTK inhibitors, Bcl-2 inhibitors

Disqualifiers: HIV, Congestive heart failure, 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: 22

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of drugs, including Nivolumab, is safe for individuals with aggressive B-cell lymphoma affecting the central nervous system (CNS). Researchers seek to assess whether these drugs can help when other treatments have failed or aren’t viable. Participants will receive several drugs in cycles over a few months. Individuals with B-cell lymphoma in the CNS that doesn’t respond to treatment or returns quickly may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take strong CYP3A inhibitors/inducers or warfarin. It's best to discuss your current medications with the study team.

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

Research has shown that the VIPOR treatment, which includes Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide, has been tested for safety in people with B-cell lymphoma. Studies have found that this combination is generally well-tolerated. Some patients experienced side effects, but these were mostly manageable. Common side effects included tiredness, low blood cell counts, and nausea. These side effects are typical for cancer treatments and can vary from person to person. Overall, the safety of VIPOR appears promising for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the VIPOR regimen for CNS-involved B-cell lymphoma because it combines several innovative drugs that work synergistically. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, VIPOR includes targeted therapies like ibrutinib and venetoclax, which specifically disrupt cancer cell survival pathways. Additionally, obinutuzumab, an engineered antibody, enhances the immune system's ability to recognize and destroy lymphoma cells. This multi-faceted approach not only aims to improve effectiveness but also potentially reduces the side effects associated with conventional treatments.

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

Research has shown that the VIPOR treatment plan, which includes venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, holds promise for treating certain aggressive B-cell lymphomas. This trial will assess the effectiveness of the VIPOR regimen in participants with CNS-involved B-cell lymphoma. Studies have found that this combination can prolong periods without cancer recurrence. In patients with relapsed diffuse large B-cell lymphoma, this treatment led to complete responses, meaning the cancer was not detectable after treatment. These drugs work together to stop cancer cells from growing. While early results are encouraging, ongoing research is needed to confirm these findings in more patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults aged 18+ with B-cell lymphoma in the CNS that's unresponsive to treatment, relapsed after treatment, or ineligible for standard therapy due to age or kidney function. Must have measurable disease and adequate organ/marrow function. Participants must not be pregnant, agree to use birth control, and can't have certain other cancers needing active treatment.

Inclusion Criteria

Participants must have evaluable disease by clinical exam and/or imaging.

I have a second cancer that doesn't need ongoing treatment.

My organs and bone marrow are working well.

Exclusion Criteria

I have had irregular heartbeats from the lower chambers of my heart.

I cannot swallow pills or have major stomach problems.

I haven't had chemotherapy, radiation, or antibody treatment in the last 7 days.

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 VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles

18 weeks

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Lenalidomide
• Obinutuzumab
• Prednisone
• Venetoclax

Trial Overview The VIPOR-Nivo trial is testing a combination of drugs (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Revlimid) on patients with primary diffuse large B-cell lymphoma of the CNS or aggressive B-cell lymphomas with secondary CNS involvement. The study involves up to six 21-day cycles of medication taken orally and by infusion.

How Is the Trial Designed?

Group I: 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) Experimental Treatment 15 Interventions

VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles

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+

Published Research Related to This Trial

Ibrutinib, idelalisib, and venetoclax are novel oral therapies for chronic lymphocytic leukemia that provide unique clinical benefits compared to traditional treatments, but they also come with specific safety concerns and logistical challenges.

Each of these agents has distinct adverse effects: ibrutinib can cause bleeding and atrial fibrillation, idelalisib may lead to hepatotoxicity, and venetoclax carries a risk of tumor lysis syndrome, necessitating careful monitoring and potential dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Chronic Lymphocytic Leukemia: Ibrutinib, Idelalisib, and Venetoclax. Waldron, M., Winter, A., Hill, BT.[2021]

Ibrutinib, idelalisib, and venetoclax are effective B cell signaling agents for treating non-Hodgkin's lymphomas, but they come with distinct toxicity profiles that differ from traditional chemotherapy.

Ibrutinib can increase the risk of atrial fibrillation and bleeding, while idelalisib requires close monitoring of liver function and infection risks, and venetoclax necessitates careful monitoring to prevent tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents. Rhodes, J., Mato, A., Sharman, JP.[2021]

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]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

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 retrospective analysis of 4 patients with relapsed/refractory mantle-cell lymphoma (MCL), the combination of ibrutinib and venetoclax resulted in a 50% complete response rate, demonstrating its potential efficacy as a treatment option.

All patients who responded to the treatment were able to undergo allogeneic stem cell transplantation, with two patients remaining in complete remission, indicating that this combination therapy may be a viable bridge to transplant for MCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in association with venetoclax for the treatment of mantle-cell lymphoma: a multicenter case series. Fabbri, A., Cencini, E., Congiu, AG., et al.[2021]

In a safety run-in cohort of 21 patients with relapsed/refractory mantle cell lymphoma, the combination of ibrutinib and venetoclax showed an impressive overall response rate of 81%, with 62% achieving a complete response after a median follow-up of 31 months.

The study indicated that concurrent administration of ibrutinib and venetoclax is safe, with only three dose-limiting toxicities observed and no new safety concerns, allowing the trial to proceed without an ibrutinib lead-in.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study. Wang, M., Ramchandren, R., Chen, R., et al.[2021]

In a retrospective study of 22 patients with chronic lymphocytic leukaemia (CLL) who progressed on ibrutinib, the combination of ibrutinib and venetoclax resulted in a median overall survival of 47.1 months, indicating potential efficacy in this challenging patient group.

For 11 patients with double-refractory CLL, the same combination therapy led to a median overall survival of 27.0 months, suggesting that this treatment may provide a valuable option for patients who have limited alternatives after failing standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined ibrutinib and venetoclax for treatment of patients with ibrutinib-resistant or double-refractory chronic lymphocytic leukaemia. Hampel, PJ., Rabe, KG., Call, TG., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05211336

Study Details | NCT05211336 | Venetoclax, Ibrutinib, ... Overall survival (OS) after VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192235/

Combination Targeted Therapy in Relapsed Diffuse Large ... We performed a single-center phase Ib/II trial of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-01104

Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and ... Researchers want to learn if a combination of drugs can help. Objective: To learn if it is safe to give people with these cancers Nivolumab (VIPOR-Nivo).

4. esmo.org esmo.org/oncology-news/vipor-regimen-associated-with-durable-remissions-in-patients-with-specific-molecular-dlbcl-subtypes

ViPOR Regimen Associated with Durable Remissions in ... The study team developed a regimen with venetoclax, ibrutinib, prednisone, and lenalidomide to target these pathways and included ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124034979

Phase 1b/2 Study of Venetoclax, Ibrutinib, Prednisone, ... We developed a fixed-duration, multi-agent targeted regimen (ViPOR) and showed it to be safe and able to induce durable complete responses (CRs) in relapsed/ ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124044719

A Pilot Study of Venetoclax, Ibrutinib, Prednisone ... We developed the multi-targeted therapy combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (VIPOR) and demonstrated curative ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/137413

Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and ... The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR). Objective: To study the safety of ViPOR for people with B-cell lymphoma ...