Venetoclax + Obinutuzumab for Leukemia

Recruiting at 525 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti CD20 antibodies

Disqualifiers: Cirrhosis, Cardiovascular disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

247 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether starting treatment with venetoclax and obinutuzumab early, before symptoms appear, is more effective for individuals with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma than waiting until symptoms develop. Venetoclax blocks a protein that helps cancer cells survive, while obinutuzumab aids the immune system in attacking the cancer. Individuals diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma within the last 18 months who have not yet received treatment might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any prior CLL-directed therapy or strong CYP3A4/5 inhibitors or inducers. It's best to discuss your current medications with the trial team.

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

Research has shown that using venetoclax and obinutuzumab together is generally safe for treating chronic lymphocytic leukemia (CLL). Long-term results indicate that this combination is effective and manageable for most patients. In a previous study, patients experienced manageable side effects, and the treatment proved effective even for those with additional health issues.

The FDA has approved this treatment for adults with CLL, confirming its strong safety record. Studies have found that serious side effects are rare, and most patients complete the treatment without major issues. Overall, the safety information is reassuring for anyone considering joining a trial with these medications. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for leukemia?

Researchers are excited about Venetoclax and Obinutuzumab for leukemia because these treatments work differently from standard options. Unlike traditional chemotherapy, Venetoclax targets a specific protein called BCL-2, which helps cancer cells survive. Obinutuzumab is an antibody that directly targets cancer cells, enhancing the immune system's ability to destroy them. This targeted approach has the potential to be more effective and cause fewer side effects than conventional chemotherapy, offering renewed hope for patients with leukemia.

What evidence suggests that venetoclax and obinutuzumab might be an effective treatment for leukemia?

Research has shown that using venetoclax and obinutuzumab together effectively treats chronic lymphocytic leukemia (CLL). In this trial, participants will receive this combination treatment, with some starting as soon as they meet eligibility criteria, while others will begin once specific indications are met. One study found that about 82% of patients survived with this combination. Another study showed it was better at eliminating tiny amounts of cancer remaining after treatment in patients who hadn't been treated before. Long-term data also demonstrate that this treatment is safe and effective, improving both survival and quality of life. This combination works by blocking proteins that cancer cells need and helping the immune system fight the cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Deborah M Stephens

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with high-risk CLL or SLL within the last year, who have not received prior CLL-directed therapy. They must have certain genetic markers, adequate organ function, and no active hepatitis B or C. Participants should be able to take oral medications and agree to quality of life assessments if they can complete forms in specified languages.

Inclusion Criteria

I do not have an active hepatitis B or C infection, or if I have latent hepatitis B, I agree to take preventive treatment.

NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

I finished treatment for autoimmune issues from CLL over 4 weeks ago.

Exclusion Criteria

I haven't had major surgery in the last 30 days or minor surgery in the last 7 days.

I am not pregnant or nursing and will use effective birth control if of reproductive age.

I do not have uncontrolled autoimmune blood disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax and obinutuzumab. Obinutuzumab is administered intravenously on specific days of the cycle, and venetoclax is taken orally daily for 12 cycles.

12 months

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and overall survival after treatment completion.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab
• Venetoclax

Trial Overview The study compares early versus delayed treatment using venetoclax (a medication that blocks a protein cancer cells need) and obinutuzumab (an antibody that helps the immune system fight cancer) in patients with newly diagnosed high-risk CLL/SLL to see which timing might lead to better outcomes.

How Is the Trial Designed?

Group I: Arm II (early V-O) Experimental Treatment 7 Interventions

Treatment begins as soon as eligibility criteria are met. Patients receive obinutuzumab IV over 4 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 22-28 of cycle 1 and on days 1-28 of cycles 2-12. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, collection of blood samples, and bone marrow aspiration and biopsy throughout the trial.

Group II: Arm I (delayed V-O) Active Control 7 Interventions

Treatment begins once 2018 IWCLL indications are met. Patients receive obinutuzumab IV over 4 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 22-28 of cycle 1 and on days 1-28 of cycles 2-12. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, collection of blood samples, and bone marrow aspiration and biopsy throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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 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 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]

Citations

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

VENCLEXTA efficacy results: 6-year overall survival 1 In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39082668/

6-year results of the randomized phase 3 CLL14 study The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL.

3. ajmc.com ajmc.com/view/6-year-data-support-fixed-duration-ven-obi-for-untreated-cll

6-Year Data Support Fixed-Duration Ven-Obi for Untreated ... Long-term data support the safety and efficacy of venetoclax (Venclexta) and obinutuzumab (Gazyva) in chronic lymphocytic leukemia (CLL).

4. onclive.com onclive.com/view/venetoclax-plus-obinutuzumab-improves-mrd-clearance-in-previously-untreated-cll

Venetoclax Plus Obinutuzumab Improves MRD Clearance ... Venetoclax plus obinutuzumab led to higher undetectable minimal residual disease rates in previously untreated chronic lymphocytic leukemia.

5. news.abbvie.com news.abbvie.com/2022-06-10-New-Data-Demonstrates-AbbVies-VENCLYXTO-R-VENCLEXTA-R-Combination-Sustained-Progression-Free-Survival-in-Chronic-Lymphocytic-Leukemia-Patients-After-Four-Years-Off-Treatment

New Data Demonstrates AbbVie's VENCLYXTO® ... The estimated overall survival (OS) rate was 81.9 percent in the VENCLYXTO/VENCLEXTA-based combination and 77.0 percent in the chlorambucil ...

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. onclive.com onclive.com/view/real-world-data-highlight-feasibility-of-venetoclax-plus-obinutuzumab-in-first-line-cll-with-comorbidities

Real-World Data Highlight Feasibility of Venetoclax Plus ... Venetoclax plus obinutuzumab generated safe and efficacious real-world outcomes in first-line CLL with comorbidities.

8. cancer.gov cancer.gov/news-events/cancer-currents-blog/2019/venetoclax-obinutuzumab-fda-approval-cll-sll

Combination Therapy with Venetoclax Approved for CLL FDA approves venetoclax (Venclexta) plus obinutuzumab (Gazyva) for the initial treatment of adults with chronic lymphocytic leukemia, ...

9. targetedonc.com targetedonc.com/view/cristallo-study-of-venetoclax-obinutuzumab-achieves-superior-mrd-in-cll

CRISTALLO Study of Venetoclax/Obinutuzumab Achieves ... The CRISTALLO trial showed that venetoclax plus obinutuzumab achieved high minimal residual disease negativity as a frontline chronic lymphocytic leukemia ...