ViPOR for Lymphoma

Overseen By Christopher J Melani, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Active CNS lymphoma, HIV, 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: 10

Duration: 18 weeks

145 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of drugs to assess their effectiveness and safety in treating B-cell lymphoma, a cancer affecting the immune system. The drugs being tested include venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide. Suitable candidates for this trial are those whose B-cell lymphoma has returned or not improved with previous treatments. Participants will receive these medications in cycles, with regular monitoring and check-ups throughout the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like warfarin or strong CYP3A inhibitors and inducers within 7 days before starting the trial drugs. It's best to discuss your current medications with the trial team to ensure compatibility.

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

Research has shown that the ViPOR treatment, which combines five medications, maintains a manageable safety profile for patients with extensive treatment histories. Most patients in these studies tolerated the treatment well and completed their planned cycles. Notably, there were no reports of tumor lysis syndrome, a serious condition where cancer cells break down rapidly, nor any treatment-related deaths. Although some patients required dose adjustments, this was uncommon. Overall, evidence suggests that while side effects may occur, they are typically manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the ViPOR treatment for lymphoma because it combines multiple active ingredients to enhance effectiveness against the disease. Unlike current standard treatments that often focus on a single drug or mechanism, ViPOR uses a cocktail approach, blending venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide. This combination aims to target cancer cells more comprehensively by attacking them from different angles, potentially leading to better outcomes. Moreover, the inclusion of venetoclax, which targets the BCL-2 protein to promote cancer cell death, is a unique feature that sets it apart from more traditional therapies. This multi-faceted strategy is what sparks optimism among researchers for potentially improved treatment efficacy and patient outcomes.

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

Research shows that the ViPOR treatment, a combination of five drugs, holds promise for treating B-cell lymphoma. In this trial, some participants will receive ViPOR. Studies have shown that about 60% of patients responded well to this combination. Specifically, 20% had a complete response, with no signs of cancer, and 40% had a partial response, where the cancer shrank or stopped growing. For certain types of lymphoma, ViPOR has been linked to long-lasting periods of cancer control. Another group in this trial will receive the iPOR treatment, which is similar but omits one of the drugs initially. This treatment also proved effective in studies, with 54% of patients responding and 38% achieving a complete response. These findings suggest ViPOR could be a strong option for patients whose cancer has returned or not improved after other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Christopher J Melani, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with B-cell lymphoma that has come back or hasn't improved after treatment can join. They must have had at least one prior regimen including an anti-CD20 antibody and be in good enough health to participate. Women who can bear children and men must agree to use contraception, and all participants need counseling on lenalidomide risks regularly.

Inclusion Criteria

My lymphoma is confirmed to be of B-cell type by a pathology lab.

All study participants must be registered into the mandatory Revlimid REMSTM program and be willing and able to comply with the requirements

Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I haven't taken strong CYP3A inhibitors or inducers in the last week.

I do not have any severe illnesses that could affect the study results or increase my risk.

Known allergy to both xanthine oxidase inhibitors and rasburicase, or known hypersensitivity to any of the study drugs

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 in 21-day cycles for up to 6 cycles, with one drug by IV on days 1 and 2 and the other four drugs by mouth on most days

18 weeks

6 cycles with multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits about 1 month after the last dose and then every few months for 3 years, and once a year for years 4 and 5

5 years

Regular visits every few months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Obinutuzumab
• Prednisone
• Revlimid (lenalidomide)
• Venetoclax

Trial Overview The ViPOR combination (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) is being tested for safety in treating B-cell lymphomas. Participants will receive these drugs in cycles of 21 days up to six times, with close monitoring especially after the first dose of venetoclax.

How Is the Trial Designed?

Group I: Arm 4: Dose Expansion Experimental Treatment 5 Interventions

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

Group II: Arm 3: Dose Expansion Experimental Treatment 5 Interventions

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Group III: Arm 2: Dose Escalation Experimental Treatment 5 Interventions

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Group IV: Arm 1: Dose Escalation Experimental Treatment 5 Interventions

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

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

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 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 II CAPTIVATE study, previously untreated patients with chronic lymphocytic leukemia (CLL) who had higher-risk features (such as unmutated IGHV status, del(17p), or TP53 mutation) showed similar efficacy and safety outcomes when treated with a combination of ibrutinib and venetoclax.

This suggests that the fixed-duration treatment with ibrutinib and venetoclax is effective and safe for both higher-risk and lower-risk CLL patients, indicating its potential as a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CAPTIVATEing Analysis for Higher-Risk CLL. Rogers, KA.[2023]

Obinutuzumab (Gazyva) is an effective treatment for chronic lymphocytic leukemia, targeting specific cancer cells to improve patient outcomes.

Ibrutinib (Imbruvica) is used for mantle-cell lymphoma and works by inhibiting a protein that helps cancer cells survive, while sofosbuvir (Sovaldi) effectively treats chronic hepatitis C by blocking the virus's ability to replicate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

The combination of venetoclax with bendamustine-rituximab (BR) was found to be safe and tolerable in a study of 60 patients with relapsed/refractory non-Hodgkin's lymphoma, with the recommended phase II dose established at 800 mg daily.

The overall response rate to the treatment was 65%, with a median duration of response of 38.3 months, indicating preliminary efficacy for this combination therapy in managing B-cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. de Vos, S., Swinnen, LJ., Wang, D., et al.[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]

The combination of venetoclax and obinutuzumab has been approved as a superior first-line treatment for elderly, unfit patients with chronic lymphocytic leukaemia (CLL), showing better efficacy than chlorambucil/obinutuzumab based on a phase-III trial.

For patients with high-risk features like deletion 17p or TP53 mutations, targeted therapies such as ibrutinib or venetoclax/obinutuzumab are recommended due to their poor response to traditional chemotherapy, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current diagnosis and treatment of chronic lymphocytic leukaemia]. Cramer, P., von Tresckow, J., Eichhorst, B., et al.[2021]

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]

Ibrutinib (Imbruvica) is an effective treatment for chronic lymphocytic leukemia, targeting specific pathways to inhibit cancer cell growth.

Tasimelteon (Hetlioz) is beneficial for individuals with non-24-hour sleep-wake disorder, helping to regulate sleep patterns, while anti-inhibitor coagulant complex (Feiba) is used to prevent or reduce bleeding episodes in patients with hemophilia A or B, demonstrating its efficacy in managing bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6494/527488/Real-World-Evidence-of-Venetoclax-Ibrutinib

Real-World Evidence of Venetoclax, Ibrutinib, Prednisone ... Overall, 60% (9/15) of patients with evaluable imaging-based response assessment responded to VIPOR(P), with 20% (3/15) achieving a CR and 40% ( ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38899693/

Combination Targeted Therapy in Relapsed Diffuse Large B ... Conclusions: Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03223610

Study Details | NCT03223610 | Venetoclax, Ibrutinib, ... The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR). Objective: To study the safety of ViPOR for people with B-cell lymphoma ...

4. 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/ ...

5. healthtree.org healthtree.org/dlbcl/community/articles/vipor-study-for-relapsed-refractory-dlbcl

ViPOR Study for Relapsed/Refractory DLBCL The ViPOR regimen is distinctive as it consists of multiple targeted agents, including venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide.

6. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper194482.html

Paper: A Pilot Study of Venetoclax, Ibrutinib, Prednisone, ... VIPOR is a synergistic combination that overcomes resistance to both chemotherapy and prior treatment with BTKi. Here, we show results of a ...