465 Participants Needed

Venetoclax + Ibrutinib + Obinutuzumab for Chronic Lymphocytic Leukemia

Recruiting at 963 trial locations
SB
Overseen ByShannon B. Keating
Age: 65+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Cancer Institute (NCI)
Must be taking: Ibrutinib, Obinutuzumab
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

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. The addition of venetoclax to the usual treatment might prevent chronic lymphocytic leukemia from returning. This trial also will investigate whether patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. 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. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia compared to ibrutinib and obinutuzumab.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. If you are on warfarin, you must stop it at least 10 days before starting the study. If you are taking strong CYP3A inhibitors or inducers, you need to stop them 14 days before joining.

Is the combination of Venetoclax, Ibrutinib, and Obinutuzumab safe for treating chronic lymphocytic leukemia?

The combination of Venetoclax, Ibrutinib, and Obinutuzumab has been shown to be generally safe in humans, with manageable side effects. Notable side effects include neutropenia (low white blood cell count), which can be managed with supportive care and dose adjustments. Overall, these treatments have been well-tolerated in clinical trials for chronic lymphocytic leukemia and other conditions.12345

What makes the drug combination of Venetoclax, Ibrutinib, and Obinutuzumab unique for treating chronic lymphocytic leukemia?

This drug combination is unique because it combines three powerful agents that target different aspects of chronic lymphocytic leukemia (CLL) and has shown superior progression-free survival compared to some traditional treatments. It is particularly beneficial for patients who have not responded to other treatments, offering a new option for those with resistant forms of CLL.23567

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

Research shows that the combination of Venetoclax and Ibrutinib improves outcomes in patients with chronic lymphocytic leukemia compared to traditional chemoimmunotherapy. Additionally, Venetoclax combined with Obinutuzumab has been shown to result in longer progression-free survival and higher response rates in untreated patients.12367

Who Is on the Research Team?

JA

Jennifer A Woyach

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for older patients (65+) with untreated chronic lymphocytic leukemia who meet specific health criteria, such as certain blood cell counts and organ function. They must not have had previous CLL treatments except for steroids or rituximab for autoimmune complications, and they should be able to swallow pills without significant gastrointestinal issues.

Inclusion Criteria

I am 65 years old or older.
I had hepatitis C but have been treated and now have no detectable virus.
My condition is intermediate risk with enlarged lymph nodes or liver/spleen but no anemia or low platelets.
See 33 more

Exclusion Criteria

I am not taking, or have stopped taking, strong CYP3A4/5 inducers for the last 14 days.
I have never had Richter's transformation or prolymphocytic leukemia.
I have not received treatment for CLL/SLL, except for steroids or specific autoimmune treatments.
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib and obinutuzumab, with venetoclax added in Arm II, for up to 14 cycles of 28 days each

56 weeks

Maintenance/Observation

Participants in Arm I continue ibrutinib, while Arm II participants achieving BM MRD negative CR undergo observation

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

  • Ibrutinib
  • Obinutuzumab
  • Venetoclax
Trial Overview The study tests adding Venetoclax, a BCL-2 inhibitor that may block cancer cell survival proteins, to the usual treatment of Ibrutinib and Obinutuzumab in treating CLL. It will also explore if patients can stop taking Ibrutinib after one year if no detectable CLL remains.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (ibrutinib, obinutuzumab, venetoclax)Experimental Treatment4 Interventions
Group II: Arm I (ibrutinib, obinutuzumab)Active Control2 Interventions

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Imbruvica for:
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Approved in United States as Imbruvica for:
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Approved in Canada as Imbruvica for:
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Approved in Japan as Imbruvica for:

Find a Clinic Near You

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

In a phase 3 trial with 523 patients, the combination of ibrutinib and venetoclax significantly improved progression-free survival compared to the traditional FCR treatment, with only 12 patients experiencing disease progression or death in the ibrutinib-venetoclax group versus 75 in the FCR group.
The study also found that 65.9% of patients on ibrutinib-venetoclax achieved undetectable measurable residual disease (MRD) in bone marrow after 5 years, indicating effective disease control, although there was a higher incidence of serious cardiac adverse events in this group compared to FCR.
Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease.Munir, T., Cairns, DA., Bloor, A., et al.[2023]
The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.
Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.
Chronic lymphocytic leukemia at ASH 2017.Wanner, D., Steurer, M.[2020]
In a retrospective study of 22 patients with chronic lymphocytic leukaemia (CLL) who progressed on ibrutinib, the combination of ibrutinib and venetoclax resulted in a median overall survival of 47.1 months, indicating potential efficacy in this challenging patient group.
For 11 patients with double-refractory CLL, the same combination therapy led to a median overall survival of 27.0 months, suggesting that this treatment may provide a valuable option for patients who have limited alternatives after failing standard therapies.
Combined ibrutinib and venetoclax for treatment of patients with ibrutinib-resistant or double-refractory chronic lymphocytic leukaemia.Hampel, PJ., Rabe, KG., Call, TG., et al.[2022]

Citations

Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. [2023]
Chronic lymphocytic leukemia at ASH 2017. [2020]
Combined ibrutinib and venetoclax for treatment of patients with ibrutinib-resistant or double-refractory chronic lymphocytic leukaemia. [2022]
Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. [2023]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. [2021]
Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. [2022]
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