ViPOR for Lymphoma

Overseen by Christopher J Melani, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Active CNS lymphoma, HIV, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of five drugs (ViPOR) to treat adults with B-cell lymphoma that has come back or not responded to other treatments. The drugs work together to block cancer cell survival mechanisms. One of the drugs, Venetoclax, is already used for another type of blood cancer and is being studied for its effectiveness in this treatment. The study aims to find the safest dose and see how well the treatment works.

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.

What data supports the effectiveness of the drugs used in the ViPOR for Lymphoma trial?

Research shows that the combination of ibrutinib, obinutuzumab, and venetoclax is effective in treating mantle cell lymphoma, with high response rates and good tolerance. Additionally, ibrutinib and venetoclax have shown promising results in improving outcomes for chronic lymphocytic leukemia. ^{1 2 3 4 5}

Is the ViPOR treatment generally safe for humans?

The combination of ibrutinib, obinutuzumab, and venetoclax has been shown to be well tolerated in patients with mantle cell lymphoma, with no dose-limiting toxicity reported. Venetoclax, when used with obinutuzumab, has an acceptable safety profile in chronic lymphocytic leukemia, with manageable side effects like neutropenia (low white blood cell count). ^{1 2 4 6 7}

What makes the ViPOR treatment for lymphoma unique?

The ViPOR treatment for lymphoma is unique because it combines multiple drugs, including ibrutinib, obinutuzumab, prednisone, lenalidomide, and venetoclax, which have shown synergy in other lymphomas like mantle cell lymphoma, potentially offering high response rates and effective disease control. ^{1 4 5 8 9}

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 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.

I do not have another active cancer that could interfere with the study.

Trial Timeline

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

Treatment Details

Interventions

• Ibrutinib (BTK Inhibitor)
• Obinutuzumab (Monoclonal Antibodies)
• Prednisone (Corticosteroid)
• Revlimid (lenalidomide) (Immunomodulatory Agent)
• Venetoclax (BCL-2 Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

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]

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]

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]

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]

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]

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]

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]

References

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

Chronic lymphocytic leukemia at ASH 2017. [2020]

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

Pharmaceutical approval update. [2021]

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

Pharmaceutical approval update. [2021]

4. 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]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

[Current diagnosis and treatment of chronic lymphocytic leukaemia]. [2021]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. [2021]

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

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