Obinutuzumab + Venetoclax vs. Chlorambucil for Chronic Lymphocytic Leukemia

Recruiting at 205 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Warfarin, Marcumar, Phenprocoumon, others

Disqualifiers: Richter's transformation, PML, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

445 Participants Needed

Trial Summary

What is the purpose of this trial?

This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in participants with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The time on study treatment was approximately one year and the follow-up period will be up to 9 years

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as warfarin and some drugs that affect liver enzymes, at least 7 days before starting the study. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

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

Research shows that the combination of Obinutuzumab and Venetoclax is effective for treating Chronic Lymphocytic Leukemia (CLL), as it leads to longer progression-free survival and higher response rates compared to the combination of Chlorambucil and Obinutuzumab. This combination is particularly beneficial for patients who cannot undergo intensive chemotherapy. ^{1 2 3 4 5}

Is the combination of Obinutuzumab and Venetoclax safe for treating Chronic Lymphocytic Leukemia?

The combination of Obinutuzumab and Venetoclax has an acceptable safety profile for treating Chronic Lymphocytic Leukemia, with manageable side effects such as neutropenia (low white blood cell count), which can be addressed with supportive care and dose adjustments. ^{1 2 3 6 7}

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

The combination of Obinutuzumab and Venetoclax is unique because it offers a chemotherapy-free option for treating chronic lymphocytic leukemia, with a fixed-duration regimen that has shown to improve progression-free survival and response rates compared to traditional chemoimmunotherapy with Chlorambucil. Venetoclax works by selectively inhibiting a protein that helps cancer cells survive, making it a novel approach in targeting leukemia cells. ^{1 2 3 7 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with untreated chronic lymphocytic leukemia (CLL) who have a life expectancy over 6 months and require treatment. They should not have severe other illnesses, must be able to use effective contraception, and cannot have central nervous system involvement or uncontrolled autoimmune conditions.

Inclusion Criteria

I have chronic lymphocytic leukemia that has not been treated before.

Life expectancy > 6 months

My blood cell counts are good without needing extra help, unless it's because of my CLL.

Exclusion Criteria

Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)

I am not infected with HIV or HTLV-1.

I haven't had a serious infection needing treatment in the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab for 6 cycles and either venetoclax or chlorambucil for 12 cycles, with each cycle comprising 28 days

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 years

Treatment Details

Interventions

• Chlorambucil
• Obinutuzumab
• Venetoclax

Trial Overview The study compares two treatments for CLL: Obinutuzumab combined with Venetoclax versus Obinutuzumab with Chlorambucil. It's an open-label, multicenter trial where participants are randomly assigned to either regimen for about one year, followed by up to nine years of follow-up.

Participant Groups

Group I: Safety Run-in Obinutuzumab + Venetoclax Experimental Treatment 2 Interventions

Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.

Group II: Obinutuzumab + Venetoclax Experimental Treatment 2 Interventions

Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.

Group III: Obinutuzumab + Chlorambucil Experimental Treatment 2 Interventions

Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

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

German CLL Study Group

Collaborator

Trials

49

Recruited

21,400+

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]

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 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]

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 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]

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]

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

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]

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

Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. [2022]

5. 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]

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

Venetoclax: First Global Approval. [2018]

7. France pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Probabilistic Cost-Effectiveness Analysis of Venetoclax and Obinutuzumab as a First-Line Therapy in Chronic Lymphocytic Leukemia in Canada. [2023]