Venetoclax + Obinutuzumab/Acalabrutinib for Chronic Lymphocytic Leukemia

Recruiting at 59 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must be taking: Venetoclax

Disqualifiers: Active infection, Richter's transformation, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

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 the safety of venetoclax in combination with obinutuzumab or acalabrutinib in the treatment of CLL. Adverse events and change in disease activity will be assessed. Venetoclax in combination with obinutuzumab or acalabrutinib is being investigated in the treatment of CLL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Participants will receive oral venetoclax in combination with intravenously (IV) infused obinutuzumab or oral acalabrutinib at in different dosing schemes as part of treatment. Approximately 120 adult participants with CLL who are being treated with venetoclax will be enrolled in the study in approximately 80 sites worldwide. Participants in Arm A will receive oral venetoclax in combination with IV infused obinutuzumab, with a 5 week venetoclax ramp up. Participants in Arm B will receive oral venetoclax in combination with oral acalabrutinib, with a 5 week venetoclax ramp up. Participants in Arm C and Arm D will receive oral venetoclax in combination with oral acalabrutinib, with differing venetoclax ramp up periods. The total study duration is approximately 28 months. 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 your current medications. It's best to discuss this with the study doctors to understand how your current medications might interact with the trial treatments.

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

Research shows that the combination of Venetoclax and Obinutuzumab is effective for treating Chronic Lymphocytic Leukemia, leading to longer progression-free survival and higher rates of undetectable minimal residual disease compared to other treatments. Additionally, Acalabrutinib, when used with Venetoclax and Obinutuzumab, is hypothesized to induce deep and durable remissions. ^{1 2 3 4 5}

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

The combination of Venetoclax and Obinutuzumab has been shown to be generally safe for treating chronic lymphocytic leukemia, with manageable side effects like neutropenia (a low level of white blood cells). Acalabrutinib, when added to this combination, is also considered effective and safe, although specific safety data for the triplet combination is less detailed. ^{1 2 3 4 6}

What makes the drug combination of Venetoclax, Obinutuzumab, and Acalabrutinib unique for treating chronic lymphocytic leukemia?

This drug combination is unique because it combines continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax and obinutuzumab, aiming for deep and long-lasting remissions by targeting minimal residual disease (MRD), which means reducing the number of cancer cells to very low levels. ^{1 2 3 4 6}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with previously untreated chronic lymphocytic leukemia (CLL) who need treatment and have a life expectancy over 6 months. They should be able to perform daily activities with ease or some difficulty (ECOG <=2), have good marrow function, and adequate kidney function (CrCl >=30 mL/min). Those with very large lymph nodes (>5 cm) and lower kidney function (CrCl <80 mL/min) can't join.

Inclusion Criteria

I can take care of myself and am up and about more than 50% of my waking hours.

I have untreated small lymphocytic lymphoma that requires treatment.

My blood cell counts are stable without needing extra help, unless it's due to my CLL.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral venetoclax in combination with intravenously infused obinutuzumab or oral acalabrutinib with a ramp-up period

5 weeks ramp-up, total treatment up to 28 months

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acalabrutinib (BTK Inhibitor)
• Obinutuzumab (Monoclonal Antibodies)
• Venetoclax (BCL-2 Inhibitor)

Trial Overview The trial is testing the safety of venetoclax combined with obinutuzumab or acalabrutinib in treating CLL. Participants are divided into four groups receiving different combinations and dosing schedules of these drugs orally or through IV infusion. The study will last about 28 months across roughly 80 global sites.

Participant Groups

Group I: Arm D: Venetoclax + Acalabrutinib Experimental Treatment 2 Interventions

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.

Group II: Arm C: Venetoclax + Acalabrutinib Experimental Treatment 2 Interventions

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.

Group III: Arm B: Venetoclax + Acalabrutinib Experimental Treatment 2 Interventions

Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.

Group IV: Arm A: Venetoclax + Obinutuzumab Experimental Treatment 2 Interventions

Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.

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

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]

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]

In a phase 2 trial involving 70 patients with chronic lymphocytic leukaemia, both 12 cycles of venetoclax consolidation and minimal residual disease-guided consolidation showed similar effectiveness, with around 50% of patients achieving undetectable minimal residual disease in bone marrow after treatment.

While consolidation treatment did not lead to treatment-related deaths, it was associated with a higher incidence of adverse events, particularly infections, indicating that while it may extend treatment duration, it does not significantly improve disease response or reduce relapse risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial. Kersting, S., Dubois, J., Nasserinejad, K., et al.[2022]

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]

In a retrospective study of 14 patients with chronic lymphocytic leukemia (CLL) treated with the venetoclax and obinutuzumab (VenG) regimen, 73% developed grade 3 or 4 neutropenia, indicating a high incidence of this side effect.

The study suggests that the high rate of neutropenia may be linked to patients having more comorbidities and high-risk disease features, highlighting the need for further research on supportive treatments to manage this side effect and allow for optimal dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. Samuels, C., Abbott, D., Niemiec, S., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. [2021]

3. 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]

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

Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

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

Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. [2022]