Venetoclax + Obinutuzumab for Chronic Lymphocytic Leukemia

(ReVenG Trial)

Recruiting at 85 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must be taking: Venetoclax, Anti-CD20 antibody

Disqualifiers: Intervening CLL treatment, 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: Unknown

Duration: 24-48 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for individuals with chronic lymphocytic leukemia (CLL), a common type of blood cancer. The researchers aim to evaluate the effectiveness of retreatment with venetoclax (a targeted therapy) and obinutuzumab (an antibody therapy) for those whose CLL symptoms have returned after earlier treatment. Participants will undergo cycles of these drugs and will be monitored for side effects and disease activity. This trial may suit those who have been off venetoclax for more than a year and have not received other treatments since. Participants should expect regular hospital or clinic visits for check-ups and evaluations. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does require that you have not received any other treatment for CLL after your previous venetoclax regimen.

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

Research has shown that the combination of venetoclax and obinutuzumab (VenG) is generally safe for treating chronic lymphocytic leukemia (CLL). In earlier studies, patients who received this treatment experienced manageable side effects, such as low white blood cell counts and infections, which are common with many cancer treatments.

The combination of venetoclax and obinutuzumab has proven effective and safe over six years. This long-term evidence suggests that most patients tolerate the treatment well. Since the FDA has already approved venetoclax for CLL, its safety is well-known. Additionally, studies in real-world settings have shown similar safety results to those in controlled clinical trials.

Overall, while some side effects exist, research considers the treatment safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of venetoclax and obinutuzumab for treating Chronic Lymphocytic Leukemia (CLL) because it offers a targeted approach that differs from the current standard treatments like chemotherapy and monoclonal antibodies alone. Venetoclax works by inhibiting the BCL-2 protein, which helps cancer cells survive, effectively leading to their death. Meanwhile, obinutuzumab is a monoclonal antibody that targets the CD20 protein on cancer cells, marking them for destruction by the immune system. This combination not only targets CLL cells directly but also enhances the immune system's ability to eliminate them, potentially leading to deeper and more sustained remissions.

What is the effectiveness track record for venetoclax and obinutuzumab in treating chronic lymphocytic leukemia?

Research has shown that using venetoclax and obinutuzumab together effectively treats chronic lymphocytic leukemia (CLL). One study found this combination reduced the small number of cancer cells that can remain after treatment more effectively than other options. Long-term results indicate that venetoclax and obinutuzumab help CLL patients live longer and improve their quality of life. The CRISTALLO trial confirmed that this treatment leaves fewer cancer cells in the body. Strong evidence supports the effectiveness of this combination for treating CLL. Participants in this trial will receive venetoclax and obinutuzumab in varying treatment durations to further evaluate their effectiveness. ^{5 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with recurring Chronic Lymphocytic Leukemia (CLL) who've previously responded to venetoclax-obinutuzumab treatment. Eligible participants are divided into two groups based on the time since their last dose and disease progression: more than 24 months for Cohort 1, or between 12-24 months for Cohort 2. Those who received other CLL treatments after VenG are excluded.

Inclusion Criteria

It's been over 24 months since my last venetoclax dose for Cohort 1, or 12-24 months for Cohort 2, and my disease progressed after first-line treatment.

I have chronic lymphocytic leukemia needing treatment based on iwCLL 2018 criteria.

I completed a specific treatment for my cancer and it improved.

Exclusion Criteria

I've had treatment for CLL after my venetoclax and anti-CD20 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) obinutuzumab + oral venetoclax (VenG) in 28-day cycles for a total of 6 cycles per cohort, followed by 6 to 18 cycles of venetoclax alone, for a total treatment of 12 to 24 cycles, depending on the cohort

24-48 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab
• Venetoclax

Trial Overview The trial is testing retreatment with oral venetoclax and IV obinutuzumab in patients whose CLL returned after initial therapy. Participants will undergo a series of treatment cycles over several months to evaluate changes in disease activity and monitor any adverse events from the medications.

How Is the Trial Designed?

Group I: Cohort 2 - venetoclax + obinutuzumab Experimental Treatment 2 Interventions

Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for eighteen 28-day cycles.

Group II: Cohort 1 - venetoclax + obinutuzumab Experimental Treatment 2 Interventions

Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for six 28-day cycles.

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

Approved in United States as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Approved in European Union as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Who Is Running the Clinical Trial?

AbbVie

Lead 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

F. Hoffmann-La Roche Ltd; German CLL Study Group (GCLLSG); Dana-Farber Cancer Institute

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

The study analyzed pharmacokinetics and exposure-response parameters of a 400 mg once-daily venetoclax regimen combined with obinutuzumab in 274 patients, confirming its suitability for first-line treatment of chronic lymphocytic leukemia (CLL).

No significant correlations were found between venetoclax exposure and progression-free survival or severe treatment-emergent adverse events, indicating that the treatment is both effective and safe at the studied dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Samineni, D., Gibiansky, L., Wang, B., et al.[2022]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

The combination of venetoclax and obinutuzumab was found to be safe and well-tolerated in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia, with no dose-limiting toxicities observed during the study.

The treatment resulted in a high overall response rate of 95% in relapsed/refractory patients and 100% in previously untreated patients, with significant rates of undetectable minimal residual disease, indicating effective disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Flinn, IW., Gribben, JG., Dyer, MJS., et al.[2021]

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 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]

In a phase 3 trial involving 432 patients with untreated chronic lymphocytic leukaemia, the combination of venetoclax plus obinutuzumab resulted in significantly longer progression-free survival compared to chlorambucil plus obinutuzumab, with a hazard ratio of 0.31, indicating a strong treatment advantage.

After a median follow-up of 39.6 months post-treatment, patients receiving venetoclax plus obinutuzumab had not yet reached median progression-free survival, while those on chlorambucil plus obinutuzumab had a median of 35.6 months, highlighting the long-term efficacy of the venetoclax regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Al-Sawaf, O., Zhang, C., Tandon, M., et al.[2020]

Venetoclax, an oral BCL-2 inhibitor, combined with obinutuzumab, has demonstrated superior efficacy compared to traditional chemoimmunotherapy in both treatment-naive and relapsed/refractory chronic lymphocytic leukemia (CLL) patients.

Obinutuzumab, a novel anti-CD20 monoclonal antibody, has been safely used with other targeted therapies like venetoclax, showing better outcomes than the older drug rituximab when paired with chlorambucil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia. Salvaris, R., Opat, S.[2021]

Citations

1. venclextahcp.com venclextahcp.com/cll/efficacy/ven-g/data.html

VENCLEXTA efficacy results: 6-year overall survival 1 VEN+G was studied against GClb in 432 patients with previously untreated CLL with comorbid medical conditions (total CIRS score >6 or CrCl <70 mL/min).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39082668/

6-year results of the randomized phase 3 CLL14 study The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL.

3. targetedonc.com targetedonc.com/view/cristallo-study-of-venetoclax-obinutuzumab-achieves-superior-mrd-in-cll

CRISTALLO Study of Venetoclax/Obinutuzumab Achieves ... The CRISTALLO trial showed that venetoclax plus obinutuzumab achieved high minimal residual disease negativity as a frontline chronic lymphocytic leukemia ...

4. ajmc.com ajmc.com/view/6-year-data-support-fixed-duration-ven-obi-for-untreated-cll

6-Year Data Support Fixed-Duration Ven-Obi for Untreated ... Long-term data support the safety and efficacy of venetoclax (Venclexta) and obinutuzumab (Gazyva) in chronic lymphocytic leukemia (CLL).

5. onclive.com onclive.com/view/venetoclax-plus-obinutuzumab-improves-mrd-clearance-in-previously-untreated-cll

Venetoclax Plus Obinutuzumab Improves MRD Clearance ... Venetoclax plus obinutuzumab achieved higher undetectable MRD rates than FCR/BR in untreated CLL patients without 17p deletions or TP53 ...

6. venclextahcp.com venclextahcp.com/cll/side-effects/ven-g-safety-profile.html

VEN+G Safety Data for CLL/SLL - venclexta No ongoing treatment exposure1. The fixed duration of VEN+G results in limited treatment exposure. VEN+G safety from the CLL14 trial.

7. ashpublications.org ashpublications.org/blood/article/144/18/1924/516941/Venetoclax-obinutuzumab-for-previously-untreated

6-year results of the randomized phase 3 CLL14 study | Blood Key PointsOne-year fixed-duration Ven-Obi results in durable treatment-free remissions, with a 6-year PFS rate of 53% and TTNT rate of 65%, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12381400/

Real-World Safety and Efficacy of Venetoclax in Chronic ... In conclusion, patients with CLL treated with venetoclax in a RW clinical setting exhibit similar efficacy and safety outcomes to those observed in RCTs. 1.

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213093

First-Line Venetoclax Combinations in Chronic ... Venetoclax–obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL.