Acalabrutinib + Venetoclax/Obinutuzumab for Chronic Lymphocytic Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ohio State University Comprehensive Cancer Center
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: High-risk disease, CNS involvement, cardiovascular disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests whether acalabrutinib in combination with venetoclax or obinutuzumab works to shrink tumors in patients with treatment-naive chronic lymphocytic leukemia . Acalabrutinib is also an inhibitor that works in the body to block the activation of certain cells that lead to the growth of cancerous B cells. 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. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib in combination with venetoclax or obinutuzumab may help ease symptoms, decrease the amount of cancer suggestive of improvement, prolonged disease-free remission and/or survival, and increased knowledge about cancer treatment in patients with chronic lymphocytic leukemia. Patients will be treated with acalabrutinib for 12 cycles, and then randomized to receive 6 cycles of acalabrutinib plus obinutuzumab or acalabrutinib plus venetoclax.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs that affect liver enzymes (CYP3A inhibitors or inducers) within 7 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination Acalabrutinib, Venetoclax, and Obinutuzumab for treating chronic lymphocytic leukemia?
Research shows that the combination of Venetoclax and Obinutuzumab is effective for treating chronic lymphocytic leukemia, leading to longer periods without disease progression and higher response rates compared to other treatments. Additionally, using Acalabrutinib with Venetoclax and Obinutuzumab may result in deep and lasting remissions.
12345Is the combination of Acalabrutinib, Venetoclax, and Obinutuzumab safe for treating chronic lymphocytic leukemia?
The combination of Venetoclax and Obinutuzumab has been shown to be generally safe for treating chronic lymphocytic leukemia, with manageable side effects like neutropenia (a low level of white blood cells). Acalabrutinib, when used with Venetoclax and Obinutuzumab, is also considered safe, but patients should be aware of potential side effects and discuss them with their doctor.
12345What makes the drug combination of Acalabrutinib, Venetoclax, and Obinutuzumab unique for treating chronic lymphocytic leukemia?
This drug combination is unique because it combines continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax and obinutuzumab, aiming for deep and durable remissions by targeting minimal residual disease (MRD). This approach is different from traditional chemoimmunotherapy, offering a chemotherapy-free option that can lead to more patients achieving undetectable MRD.
12346Eligibility Criteria
Adults diagnosed with chronic lymphocytic leukemia who haven't had previous cancer treatments, except for certain conditions like autoimmune diseases or symptom control. They must show specific symptoms or blood abnormalities as per iwCLL guidelines, have adequate organ function, and women of childbearing age must use effective contraception.Inclusion Criteria
I am 18 years old or older.
Woman of childbearing potential must use contraception
Willing and able to participate in all required evaluations and procedures in this study protocol
+5 more
Exclusion Criteria
Hepatitis B or C serologic status
I have uncontrolled autoimmune blood disorders.
I am on blood thinners like warfarin.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive acalabrutinib for 12 cycles, followed by randomization to receive 6 cycles of acalabrutinib plus either obinutuzumab or venetoclax
18 cycles (approximately 18 months)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 10 years
Follow-up at 30 days and every 6 months
Participant Groups
The trial is testing acalabrutinib combined with either venetoclax or obinutuzumab to see if they can shrink tumors in patients with untreated chronic lymphocytic leukemia. Patients will first receive acalabrutinib alone, then be randomly assigned to add one of the other drugs for further treatment cycles.
2Treatment groups
Experimental Treatment
Group I: Arm II (acalabrutinib, venetoclax)Experimental Treatment2 Interventions
Patients receive acalabrutinib PO BID on days 1-28. Patients also receive venetoclax PO QD on days 1-28 days of cycles 13-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (acalabrutinib, obinutuzumab)Experimental Treatment2 Interventions
Patients receive acalabrutinib PO BID on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 13 and day 1 of cycles 14-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
Acalabrutinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Calquence for:
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
🇪🇺 Approved in European Union as Calquence for:
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
- Mantle cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Ohio State University Comprehensive Cancer CenterLead Sponsor
References
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. [2020]Venetoclax plus obinutuzumab has been established as a fixed-duration treatment regimen for patients with chronic lymphocytic leukaemia. We compared the long-term efficacy after treatment cessation of the combination of venetoclax plus obinutuzumab with chlorambucil plus obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia.
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]Venetoclax (Venclexta®; Venclyxto®) is a first-in-class, oral, selective inhibitor of B cell lymphoma 2 (BCL2). In several countries, including the USA and those of the EU, venetoclax is indicated in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). Approval was based on the results of the phase III CLL14 trial in patients with previously untreated CLL and co-existing conditions. In this study, fixed-duration (12 months) targeted treatment with venetoclax + obinutuzumab resulted in significantly longer progression-free survival (PFS; primary endpoint) relative to fixed-duration chemoimmunotherapy with chlorambucil + obinutuzumab. Venetoclax + obinutuzumab was also associated with significantly higher rates of undetectable minimal residual disease (MRD), complete response and overall response than chlorambucil + obinutuzumab. Improvements in clinical outcomes with venetoclax + obinutuzumab were maintained during long-term follow-up, when all patients had been off treatment for ≥ 2 years. No significant between-group difference was observed in overall survival (OS). Venetoclax had an acceptable tolerability profile. Notable adverse events such as grade 3 or 4 neutropenia can be managed with supportive therapy and venetoclax dose modifications. In conclusion, fixed-duration venetoclax + obinutuzumab represents an important chemotherapy-free first-line treatment option for patients with CLL, particularly those who are not fit enough to receive intensive chemoimmunotherapy.
Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. [2021]Both continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax-obinutuzumab are effective for previously untreated chronic lymphocytic leukaemia. We hypothesised that frontline time-limited, minimal residual disease (MRD)-guided triplet therapy with acalabrutinib, venetoclax, and obinutuzumab would induce deep (ie, more patients with undetectable MRD) and durable remissions.
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]Fixed-duration 12 cycles of venetoclax plus obinutuzumab is established as first-line treatment for patients with chronic lymphocytic leukaemia. We aimed to determine the activity and safety of 12 cycles of venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated patients with chronic lymphocytic leukaemia who were unfit for fludarabine-based treatment, and whether this could be guided by minimal residual disease status.
Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. [2022]The time-limited combination of venetoclax and obinutuzumab (VenG) was established by the German CLL Study Group in the CLL14 trial for the upfront management of newly diagnosed chronic lymphocytic leukemia (CLL), showing a superior progression free survival benefit. The incidence of grade 3-4 neutropenia was reported in the range of 52.8%-57.7%. However, patients who develop neutropenia with this combination have yet to be formally characterized in the literature as it has impact on the clinical practice setting.
An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia. [2021]In the last decade, the treatment of chronic lymphocytic leukemia (CLL) has shifted away from chemoimmunotherapy toward targeted novel agents such as small molecule inhibitors and antibodies. Here, we give an overview of the pharmacology of venetoclax and obinutuzumab and the evidence from early phase to Phase III trials that have shaped how they are used in the treatment of CLL. Venetoclax, an oral anti-apoptotic BCL-2 inhibitor, in combination with a CD20 antibody has shown superiority to chemoimmunotherapy in treatment-naive and relapsed/refractory CLL. Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil.