Venetoclax + Obinutuzumab for Chronic Lymphocytic Leukemia

(ReVenG Trial)

Recruiting at 73 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

Trial Summary

What is the purpose of this trial?

Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess retreatment with venetoclax-obinutuzumab (VenG) in participants previously treated with fixed duration first-line (IL) therapy of venetoclax in combination with an anti-CD20 antibody +/- X (where X is any additional drug). Adverse events and change in disease activity will be assessed. Venetoclax is an approved drug for the treatment of CLL. Study doctors put the participants in 1 of 2 groups, called cohorts, based on when symptoms of CLL came back after previous treatment in first-line. Approximately 75 adult participants with CLL who have been treated with venetoclax in combination with an anti-CD20 antibody +/- X will be enrolled in the study in approximately 60 sites worldwide. Participants will 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. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

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.

What data supports the effectiveness of the drug combination Venetoclax and Obinutuzumab for treating Chronic Lymphocytic Leukemia?

Research shows that the combination of Venetoclax and Obinutuzumab significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) compared to traditional chemoimmunotherapy in patients with previously untreated Chronic Lymphocytic Leukemia. This combination also leads to higher rates of undetectable minimal residual disease (a measure of how much cancer is left after treatment) and overall response. ^{1 2 3 4 5}

Is the combination of Venetoclax and Obinutuzumab safe for treating chronic lymphocytic leukemia?

The combination of Venetoclax and Obinutuzumab has been shown to have an acceptable safety profile for treating chronic lymphocytic leukemia. Common side effects include neutropenia (low white blood cell count), which can be managed with supportive care and dose adjustments. No dose-limiting toxicities were observed, and serious infections were rare. ^{1 2 3 4 6}

How is the drug combination of Venetoclax and Obinutuzumab unique for treating chronic lymphocytic leukemia?

The combination of Venetoclax and Obinutuzumab is unique because it offers a chemotherapy-free, fixed-duration treatment option for chronic lymphocytic leukemia, leading to longer progression-free survival and higher rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy. Venetoclax is a first-in-class oral drug that selectively inhibits BCL2, a protein that helps cancer cells survive, making this combination particularly effective for patients who cannot tolerate intensive chemotherapy. ^{1 2 3 4 7}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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, 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]

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]

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]

References

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

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

2. United States 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. [2022]

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

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

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

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia. [2021]

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

Venetoclax: First Global Approval. [2018]

7. England 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. [2020]