247 Participants Needed

Venetoclax + Obinutuzumab for Leukemia

Recruiting at 486 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

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.

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 option for treating chronic lymphocytic leukemia, particularly for patients who are not fit for intensive chemoimmunotherapy. This treatment targets cancer cells more precisely by inhibiting BCL2, a protein that helps cancer cells survive, and has shown higher rates of undetectable minimal residual disease and longer progression-free survival compared to traditional chemoimmunotherapy.12345

Research Team

DM

Deborah M Stephens

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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.
See 26 more

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.
See 10 more

Timeline

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

Treatment Details

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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (early V-O)Experimental Treatment7 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 Control7 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

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

References

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
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]
Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. [2022]
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. [2021]