Venetoclax + Obinutuzumab for Chronic Lymphocytic Leukemia
(ReVenG Trial)
Recruiting in Palo Alto (17 mi)
+72 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AbbVie
Must be taking: Venetoclax, Anti-CD20 antibody
Disqualifiers: Intervening CLL treatment, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess retreatment with venetoclax-obinutuzumab (VenG) in participants previously treated with fixed duration first-line (IL) therapy of venetoclax in combination with an anti-CD20 antibody +/- X (where X is any additional drug). Adverse events and change in disease activity will be assessed.
Venetoclax is an approved drug for the treatment of CLL. Study doctors put the participants in 1 of 2 groups, called cohorts, based on when symptoms of CLL came back after previous treatment in first-line. Approximately 75 adult participants with CLL who have been treated with venetoclax in combination with an anti-CD20 antibody +/- X will be enrolled in the study in approximately 60 sites worldwide.
Participants will receive intravenous (IV) obinutuzumab + oral venetoclax (VenG) in 28-day cycles for a total of 6 cycles per cohort, followed by 6 to 18 cycles of venetoclax alone, for a total treatment of 12 to 24 cycles, depending on the cohort.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it does require that you have not received any other treatment for CLL after your previous venetoclax regimen.
What data supports the effectiveness of the drug combination Venetoclax and Obinutuzumab for treating Chronic Lymphocytic Leukemia?
Research shows that the combination of Venetoclax and Obinutuzumab significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) compared to traditional chemoimmunotherapy in patients with previously untreated Chronic Lymphocytic Leukemia. This combination also leads to higher rates of undetectable minimal residual disease (a measure of how much cancer is left after treatment) and overall response.
12345Is the combination of Venetoclax and Obinutuzumab safe for treating chronic lymphocytic leukemia?
The combination of Venetoclax and Obinutuzumab has been shown to have an acceptable safety profile for treating chronic lymphocytic leukemia. Common side effects include neutropenia (low white blood cell count), which can be managed with supportive care and dose adjustments. No dose-limiting toxicities were observed, and serious infections were rare.
12346How 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, fixed-duration treatment option for chronic lymphocytic leukemia, leading to longer progression-free survival and higher rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy. Venetoclax is a first-in-class oral drug that selectively inhibits BCL2, a protein that helps cancer cells survive, making this combination particularly effective for patients who cannot tolerate intensive chemotherapy.
12347Eligibility Criteria
Adults with recurring Chronic Lymphocytic Leukemia (CLL) who've previously responded to venetoclax-obinutuzumab treatment. Eligible participants are divided into two groups based on the time since their last dose and disease progression: more than 24 months for Cohort 1, or between 12-24 months for Cohort 2. Those who received other CLL treatments after VenG are excluded.Inclusion Criteria
It's been over 24 months since my last venetoclax dose for Cohort 1, or 12-24 months for Cohort 2, and my disease progressed after first-line treatment.
I have chronic lymphocytic leukemia needing treatment based on iwCLL 2018 criteria.
I completed a specific treatment for my cancer and it improved.
Exclusion Criteria
I've had treatment for CLL after my venetoclax and anti-CD20 therapy.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intravenous (IV) obinutuzumab + oral venetoclax (VenG) in 28-day cycles for a total of 6 cycles per cohort, followed by 6 to 18 cycles of venetoclax alone, for a total treatment of 12 to 24 cycles, depending on the cohort
24-48 weeks
Regular visits at a hospital or clinic
Follow-up
Participants are monitored for safety and effectiveness after treatment
15 months
Participant Groups
The trial is testing retreatment with oral venetoclax and IV obinutuzumab in patients whose CLL returned after initial therapy. Participants will undergo a series of treatment cycles over several months to evaluate changes in disease activity and monitor any adverse events from the medications.
2Treatment groups
Experimental Treatment
Group I: Cohort 2 - venetoclax + obinutuzumabExperimental Treatment2 Interventions
Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for eighteen 28-day cycles.
Group II: Cohort 1 - venetoclax + obinutuzumabExperimental Treatment2 Interventions
Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for six 28-day cycles.
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
Research Locations NearbySelect from list below to view details:
Medical College of Wisconsin /ID# 233426Milwaukee, WI
Henry Ford Hospital /ID# 230268Detroit, MI
Fox Chase Cancer Center /ID# 246851Philadelphia, PA
Northwestern University Feinberg School of Medicine /ID# 230060Chicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
F. Hoffmann-La Roche Ltd; German CLL Study Group (GCLLSG); Dana-Farber Cancer InstituteCollaborator
References
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.
Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. [2022]This study aims to investigate pharmacokinetics (PK) and exposure-response parameters of the 400 mg once-daily venetoclax dose regimen in combination with obinutuzumab, which was approved for the first-line (1L) treatment of chronic lymphocytic leukemia (CLL) based on data from the phase 3 CLL14 study and the phase 1b dose-finding GP28331 study.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). .
Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. [2021]This single-arm, open-label, phase 1b study evaluated the maximum tolerated dose (MTD) of venetoclax when given with obinutuzumab and its safety and tolerability in patients with relapsed/refractory (R/R) or previously untreated (first line [1L]) chronic lymphocytic leukemia (CLL). Venetoclax dose initially was escalated (100-400 mg) in a 3 + 3 design to define MTD combined with standard-dose obinutuzumab. Patients received venetoclax (schedule A) or obinutuzumab (schedule B) first to compare safety and determine dose/schedule for expansion. Venetoclax-obinutuzumab was administered for 6 cycles, followed by venetoclax monotherapy until disease progression (R/R) or fixed duration 1-year treatment (1L). Fifty R/R and 32 1L patients were enrolled. No dose-limiting toxicities were observed. Safety, including incidence of tumor lysis syndrome (TLS), did not differ between schedules (2 laboratory TLSs per schedule). Schedule B and a 400-mg dose of venetoclax were chosen for expansion. The most common grade 3-4 adverse event was neutropenia (R/R, 58% of patients; 1L, 53%). Rates of grade 3-4 infections were 29% (R/R) and 13% (1L); no fatal infections occurred in 1L. All infusion-related reactions were grade 1-2, except for 2 grade 3 events. No clinical TLS was observed. Overall best response rate was 95% in R/R (complete response [CR]/CR with incomplete marrow recovery [CRi], 37%) and 100% in 1L (CR/CRi, 78%) patients. Rate of undetectable (<10-4) minimal residual disease (uMRD) in peripheral blood for R/R and 1L patients, respectively, was 64% and 91% ≥3 months after last obinutuzumab dose. Venetoclax and obinutuzumab therapy had an acceptable safety profile and elicited durable responses and high rates of uMRD. This trial was registered at www.clinicaltrials.gov as #NCT01685892.
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.
Venetoclax: First Global Approval. [2018]Venetoclax (Venclexta™) is an oral selective inhibitor of the prosurvival protein BCL-2 and therefore restores the apoptotic ability of malignant cells. The drug arose from research by Abbott Laboratories (now AbbVie) during a collaboration with Genentech and is being co-developed by AbbVie and Genentech/Roche primarily for the treatment of haematological malignancies. Venetoclax is approved in the USA for use as monotherapy in patients with chronic lymphocytic leukaemia (CLL) with the 17p deletion (as detected by an approved FDA test) who have received at least one prior therapy, and is awaiting approval for similar indications in the EU and Canada. Venetoclax is also in phase I-III development as combination therapy for CLL, phase I/II development as monotherapy and/or combination therapy for non-Hodgkin lymphomas (including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma) and acute myeloid leukaemia, and phase I development for multiple myeloma, systemic lupus erythematosus and breast cancer. This article summarizes the milestones in the development of venetoclax leading to this first approval for CLL.
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.