Venetoclax for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

+12 other locations

Overseen by Meghan Thompson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Venetoclax

Disqualifiers: Ongoing clinical trial participation, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will find out whether people with CLL or SLL who have received treatment with venetoclax, either alone or in combination with another drug, and who are found to be MRD-negative, can stop treatment with venetoclax and remain off-treatment for 12 months or more. The researchers will also see whether study participants remain MRD-negative after they stop treatment with venetoclax.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it focuses on patients who are already receiving venetoclax-based therapy, so you may need to continue with that treatment.

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

Research shows that Venetoclax, when combined with obinutuzumab, significantly improves progression-free survival and response rates in patients with previously untreated chronic lymphocytic leukemia compared to traditional chemoimmunotherapy. Additionally, Venetoclax combined with rituximab has been effective in relapsed or refractory cases, providing durable responses and manageable side effects. ^{1 2 3 4 5}

Is venetoclax safe for treating chronic lymphocytic leukemia?

Venetoclax, used alone or with other drugs like 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 quickly) were rare and manageable. ^{3 4 5 6 7}

How does the drug venetoclax differ from other treatments for chronic lymphocytic leukemia?

Venetoclax is unique because it is an oral drug that specifically targets and inhibits BCL-2, a protein that helps cancer cells survive, making it a chemotherapy-free option. When combined with anti-CD20 monoclonal antibodies like obinutuzumab or rituximab, it has shown superior effectiveness in prolonging progression-free survival compared to traditional chemoimmunotherapy, especially in patients with certain genetic mutations or those who have relapsed. ^{3 4 5 8 9}

Research Team

Meghan Thompson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma, who have had a positive response to venetoclax treatment and show no minimal residual disease. They must have completed any anti-CD20 monoclonal antibody treatments and been on venetoclax for at least 6 months.

Inclusion Criteria

I have had a complete or partial recovery from my condition with venetoclax treatment.

My diagnosis is chronic lymphocytic leukemia or small lymphocytic lymphoma.

I can provide a sample for future cancer monitoring tests.

Exclusion Criteria

I am willing and able to follow all study requirements.

I understand the study's risks and can sign the consent form.

I am currently in a trial receiving venetoclax or an anti-CD20 drug.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4-8 weeks

2 visits (in-person)

Treatment

Participants receive venetoclax, either alone or in combination with an anti-CD20 monoclonal antibody, and are monitored for MRD status

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on maintaining MRD-negativity

24 months

Regular follow-up visits

Treatment Details

Interventions

• Anti CD20 Monoclonal Antibody (Monoclonal Antibodies)
• Venetoclax (BCL-2 Inhibitor)

Trial Overview The trial is testing if people with CLL or SLL who are MRD-negative after venetoclax treatment can stop taking the drug without their disease returning within 12 months. It also checks if they stay MRD-negative post-treatment.

Participant Groups

Group I: Venetoclax with anti-CD20 monoclonal antibody Experimental Treatment 1 Intervention

Group II: Venetoclax monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Adaptive Biotechnologies

Industry Sponsor

Trials

14

Recruited

3,700+

Findings from Research

In a study involving 10 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the addition of rituximab to venetoclax therapy resulted in a 50% response rate, with three patients achieving complete responses and two achieving partial responses.

The combination treatment was well tolerated, suggesting that adding rituximab after progression on venetoclax may provide a beneficial option for some patients with R/R CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. Handunnetti, S., Anderson, MA., Roberts, AW., et al.[2022]

In a phase 3 trial involving 926 fit patients with chronic lymphocytic leukemia (CLL), the combination of venetoclax and obinutuzumab, with or without ibrutinib, resulted in significantly higher rates of undetectable minimal residual disease at 15 months compared to traditional chemoimmunotherapy (52% vs. 86.5% and 92.2%, respectively).

The three-year progression-free survival rates were also superior for the venetoclax-obinutuzumab-ibrutinib group (90.5%) and venetoclax-obinutuzumab group (87.7%) compared to the chemoimmunotherapy group (75.5%), indicating a more effective long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. Eichhorst, B., Niemann, CU., Kater, AP., et al.[2023]

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]

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 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]

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]

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 a study of 323 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), a daily dose of 400 mg of venetoclax resulted in a median progression-free survival (PFS) of 1.8 years.

The addition of 6 cycles of rituximab to venetoclax treatment significantly increased the median PFS to 3.9 years, demonstrating a synergistic effect that enhances treatment efficacy beyond increasing the venetoclax dose alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Freise, KJ., Jones, AK., Menon, RM., et al.[2018]

References

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

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. [2022]

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

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. [2023]

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

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

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

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

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

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

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. [2018]