Rituximab + Venetoclax for Marginal Zone Lymphoma

Overseen By Emma Logan, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gottfried von Keudell, MD PhD

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Prior systemic therapy, Uncontrolled illness, 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

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

Compensation: Varies

Number of Visits: 2

33 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have taken moderate or strong CYP3A inhibitors or inducers within 7 days before starting venetoclax.

What data supports the effectiveness of the drug combination Rituximab and Venetoclax for treating Marginal Zone Lymphoma?

Research shows that the combination of Venetoclax and Rituximab is effective in treating chronic lymphocytic leukemia (CLL), with studies indicating that this combination can significantly prolong the time patients live without the disease getting worse. This suggests potential benefits for similar conditions like Marginal Zone Lymphoma. ^{1 2 3 4 5}

What makes the drug combination of Rituximab and Venetoclax unique for treating Marginal Zone Lymphoma?

The combination of Rituximab and Venetoclax is unique because it leverages the synergistic effect of these drugs, where Rituximab targets CD20 on B-cells and Venetoclax inhibits BCL-2, a protein that helps cancer cells survive. This combination has shown to significantly improve progression-free survival in similar conditions like chronic lymphocytic leukemia, suggesting potential benefits for Marginal Zone Lymphoma as well. ^{1 2 3 4 6}

What is the purpose of this trial?

The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating participants with untreated Marginal Zone Lymphoma (MZL). The names of the study drugs involved in this study are: * Venetoclax (a type of inhibitor) * Rituximab (a type of antibody)

Research Team

Gottfried von Keudell, MD, PhD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for individuals with untreated Marginal Zone Lymphoma (MZL), a type of lymphoma. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

Hemoglobin ≥8.0 g/dL

Platelets ≥50,000 cells/mm3

My liver enzymes are within normal limits, unless due to my cancer.

Exclusion Criteria

I am not eligible for radiation therapy aimed at curing early-stage stomach lymphoma linked to H. pylori.

I have been treated with ibrutinib or another BTK inhibitor.

I haven't taken strong medications like fluconazole within the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive Rituximab weekly for 4 weeks and Venetoclax daily for 4 weeks

8 weeks

Weekly visits for Rituximab, daily administration of Venetoclax

Maintenance

Participants receive Venetoclax daily and Rituximab at specified intervals, with regular scans

96 weeks

Regular visits for drug administration and scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

In-clinic visit at 1 year after finishing study drugs

Treatment Details

Interventions

• Rituximab
• Venetoclax

Trial Overview The study is testing the effectiveness of combining two drugs, Venetoclax and Rituximab, in treating MZL. Venetoclax is an inhibitor that targets cancer cells, while Rituximab is an antibody that helps the immune system attack cancer.

Participant Groups

Group I: Rituximab + Venetoclax Experimental Treatment 2 Interventions

33 participants will be enrolled and will complete study procedures as follows: * Baseline visit with screening assessments, scans, and tumor and bone marrow biopsies. * Induction Period: * CT/MRI scans at week 4. * Weeks 1 - 4: Predetermined dose of Rituximab 1x weekly. * Weeks 5 - 8: Predetermined dose of Venetoclax 1x daily. * Maintenance Period: * CT/MRI scan on weeks 12, 36, 60, 84, and then every 6 months after week 96. * Predetermined dose of Venetoclax 1x daily for up to week 96, then once every 6 months. * Predetermined dose of Rituximab 1x weekly at weeks 12, 24, 36, and 48. * End of Treatment Visit: CT/MRI scan, tumor biopsy, and bone marrow biopsy. * Follow up: In-clinic visit at 1 year after finishing study drugs.

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

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

Gottfried von Keudell, MD PhD

Lead Sponsor

Trials

2

Recruited

50+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

In a study involving 10 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the addition of rituximab to venetoclax therapy resulted in a 50% response rate, with three patients achieving complete responses and two achieving partial responses.

The combination treatment was well tolerated, suggesting that adding rituximab after progression on venetoclax may provide a beneficial option for some patients with R/R CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. Handunnetti, S., Anderson, MA., Roberts, AW., et al.[2022]

In a study of 323 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), a daily dose of 400 mg of venetoclax resulted in a median progression-free survival (PFS) of 1.8 years.

The addition of 6 cycles of rituximab to venetoclax treatment significantly increased the median PFS to 3.9 years, demonstrating a synergistic effect that enhances treatment efficacy beyond increasing the venetoclax dose alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Freise, KJ., Jones, AK., Menon, RM., et al.[2018]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

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

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

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

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. [2022]

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

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. [2018]

5. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

6. England pubmed.ncbi.nlm.nih.gov

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