Venetoclax + Obinutuzumab for Chronic Lymphocytic Leukemia

Recruiting at 15 trial locations

Overseen By Jae Park, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Warfarin, CYP3A inhibitors, others

Disqualifiers: Prior CLL therapy, Active infection, 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: 9-21 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will help researchers collect more information about how effective the combination of venetoclax and obinutuzumab is in treating CLL in people who have not received a previous treatment for their cancer.

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

The trial does not specify if you need to stop taking your current medications, but you cannot use warfarin or certain other drugs that interact with the study medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

The combination of Venetoclax and Obinutuzumab has been shown to be effective in treating Chronic Lymphocytic Leukemia (CLL), with studies indicating longer progression-free survival and higher response rates compared to traditional chemoimmunotherapy. In particular, the CLL14 trial demonstrated that this drug combination led to significant improvements in clinical outcomes, including higher rates of undetectable minimal residual disease and complete 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 in treating chronic lymphocytic leukemia. Common side effects include neutropenia (low white blood cell count), which can be managed with supportive care and dose adjustments. Serious side effects like tumor lysis syndrome (a condition where cancer cells break down rapidly) were rare and manageable. ^{1 2 4 5 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. This regimen is particularly beneficial for patients who are not fit for intensive chemotherapy. ^{1 2 4 5 7}

Research Team

Meghan Thompson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with untreated chronic lymphocytic leukemia who are generally in good health and have normal organ function. They must be able to perform daily activities with ease or only limited assistance (ECOG Performance Status of 0 or 1). Participants need to agree to use effective contraception and not donate sperm or eggs. People with a history of other cancers, significant infections, liver disease, positive tests for hepatitis B/C or HIV, recent major surgery, inability to swallow tablets, known drug allergies, or those requiring warfarin are excluded.

Inclusion Criteria

AST or ALT ≤ 2.5 x ULN

My hemoglobin level is at least 8 g/dL without needing a blood transfusion.

My blood counts are within normal ranges, not affected by my condition.

Exclusion Criteria

I had or have hidden hepatitis B but no active virus, and I agree to monthly DNA tests.

I have had treatment for CLL, but may have taken steroids for less than a week to manage symptoms.

I had surgery for early-stage, low-grade prostate cancer and currently show no signs of the disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a minimum of 9 cycles of therapy with venetoclax and obinutuzumab, with each cycle lasting 28 days. Additional 12 cycles of venetoclax monotherapy for MRD positive patients at Cycle 9.

9-21 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Obinutuzumab
• Venetoclax

Trial Overview The trial is testing the effectiveness of combining two drugs: Venetoclax and Obinutuzumab in treating CLL. The study includes adults who haven't been treated before for their cancer. It aims to gather more data on how well these drugs work together when given as an initial treatment.

Participant Groups

Group I: Venetoclax and Obinutuzumab Experimental Treatment 2 Interventions

All patients will receive a minimum of 9 cycles (cycle = 28 days) of therapy with venetoclax and obinutuzumab during the treatment period. For patients who remain MRD positive at Cycle 9 of therapy, an additional 12 cycles of venetoclax monotherapy will be given.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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]

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

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]