Venetoclax for Chronic Lymphocytic Leukemia

Recruiting at 12 trial locations

Overseen By Meghan Thompson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Venetoclax

Disqualifiers: Ongoing clinical trial participation, 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

Compensation: Varies

Number of Visits: 2

Duration: 12 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) can stop taking venetoclax and remain in remission for a year or more. Researchers are testing venetoclax alone and in combination with an anti-CD20 monoclonal antibody to determine if patients stay cancer-free after stopping treatment. This trial targets those who have already received venetoclax for at least six months and show no detectable cancer in their blood. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that venetoclax has been tested for safety in people with chronic lymphocytic leukemia (CLL). Studies have found that venetoclax treatments are generally well-tolerated by patients. For example, one study found that patients experienced fewer side effects when the treatment was administered for a set period, avoiding prolonged use.

When combined with an anti-CD20 monoclonal antibody, venetoclax's safety has also been studied. Early research suggests that this combination can be used without causing many serious side effects. In real-world studies, venetoclax, with or without these antibodies, has demonstrated a good safety record.

While venetoclax remains under investigation in trials, substantial research has already been conducted. This provides considerable evidence that it is generally safe to use, either alone or with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Venetoclax and its combination with an anti-CD20 monoclonal antibody for treating Chronic Lymphocytic Leukemia (CLL) because they offer a unique approach compared to standard therapies like chemotherapy and traditional immunotherapy. Unlike many current treatments, Venetoclax targets a specific protein called BCL-2, which helps cancer cells survive. By blocking this protein, Venetoclax promotes the death of these cancer cells. When combined with an anti-CD20 monoclonal antibody, which targets and helps eliminate cancerous B cells, this treatment not only enhances the effectiveness but also potentially reduces the side effects associated with conventional therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Studies have shown that venetoclax effectively treats chronic lymphocytic leukemia (CLL). One study found that 79% of patients with CLL, whose cancer had returned or not responded to previous treatments, experienced tumor reduction or disappearance with venetoclax alone. In this trial, some participants will receive venetoclax monotherapy, while others will receive venetoclax combined with an anti-CD20 monoclonal antibody, such as rituximab. Combining venetoclax with another drug, like rituximab, often yields even better results. More patients achieve a complete response, and sensitive tests detect no cancer cells. Overall, these findings suggest that venetoclax, especially when combined with another drug, can be a strong option for treating CLL. ^{4 5 6 7 8}

Who Is on the Research Team?

Meghan Thompson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Anti CD20 Monoclonal Antibody
• Venetoclax

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.

How Is the Trial Designed?

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

Group II: Venetoclax monotherapy Experimental Treatment 1 Intervention

Anti CD20 Monoclonal Antibody is already approved in European Union, United States for the following indications:

Approved in European Union as Rituximab for:

• Non-Hodgkin lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis

Approved in United States as Rituximab for:

• Non-Hodgkin lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as Obinutuzumab for:

• Chronic lymphocytic leukemia
• Follicular lymphoma

Approved in United States as Obinutuzumab for:

• Chronic lymphocytic leukemia
• Follicular lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Adaptive Biotechnologies

Industry Sponsor

Trials

14

Recruited

3,700+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5026291/

The potential of venetoclax (ABT-199) in chronic lymphocytic ... In the phase I trial in R/R CLL and lymphoma patients, the ORR with ibrutinib was 60%, including 16% CRs and median PFS of 13.6 months. Results varied by ...

2. venclextahcp.com venclextahcp.com/cll/efficacy/ven-g/data.html

VENCLEXTA efficacy results: 6-year overall survival 1 In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01889186?term=venetoclax&viewType=Table&rank=6

NCT01889186 | A Study of the Efficacy of ABT-199 in ... This was an open-label, multicenter, global study to determine the efficacy of ABT-199 ( Venetoclax ) monotherapy in participants with relapsed/refractory (R/R) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11253904/

An update on the efficacy of Venetoclax for chronic ... In this study, 107 patients with R/R CLL showed an overall response rate (ORR) of 79%. CR or complete remission with incomplete count recovery (CRi) was ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118526343

Venetoclax (ABT-199/GDC-0199) Monotherapy Induces ... A phase 1 study of VEN showed high response rates in pts with relapsed/refractory (R/R) CLL, including del(17p) CLL (overall response rate, ORR = 77%). This ...

6. venclextahcp.com venclextahcp.com/cll/side-effects/ven-g-safety-profile.html

VEN+G Safety Data for CLL/SLL - venclexta No ongoing treatment exposure1. The fixed duration of VEN+G results in limited treatment exposure. VEN+G safety from the CLL14 trial.

7. venclextahcp.com venclextahcp.com/cll/side-effects/ven-r-safety-profile.html

VEN+R Safety Data for CLL/SLL - venclexta VENCLEXTA-based regimens offer well-studied safety profiles with exposure limited to 2 years1* · No ongoing treatment exposure · VEN+R safety from the MURANO ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118474733

Safety and Efficacy of a Combination of Venetoclax (GDC ... We present preliminary efficacy and updated safety data from an ongoing phase 1b study (NCT01685892) evaluating this combination in R/R or treatment-naïve (TN) ...