Bcl-2 Inhibitor + Obinutuzumab + Ibrutinib for Chronic Lymphocytic Leukemia

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Kerry Rogers

Must not be taking: Warfarin, CYP3A4 inhibitors, others

Disqualifiers: Autoimmune anemia, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 14 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of a combination treatment for chronic lymphocytic leukemia (CLL), particularly for those whose CLL has returned, doesn't respond to treatment, or has never been treated. The treatment combines three drugs: GDC-0199, a Bcl-2 inhibitor that halts cancer cell growth; ibrutinib, which also blocks cancer cell growth; and obinutuzumab, an antibody targeting cancer cells. It is intended for individuals with a confirmed CLL diagnosis who have either tried at least one previous treatment and require further therapy or have symptoms but haven't received any prior treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications before starting, such as warfarin and potent CYP3A4 inhibitors or inducers. If you're on these, you may need to switch to alternatives or stop them for a specific period before joining the trial.

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

Previous studies have shown that Venetoclax (also known as GDC-0199) has a high success rate in treating chronic lymphocytic leukemia (CLL). Most patients tolerate it well, though some side effects can occur, such as low white blood cell counts, which increase infection risk.

Research has shown that Ibrutinib is also a well-tolerated treatment for CLL. Long-term studies have not identified any new major safety issues, but some patients may experience side effects like diarrhea, tiredness, and low blood platelet counts.

Studies indicate that Obinutuzumab, whether used alone or with other treatments, can cause serious side effects. The most common are low white blood cell counts, low red blood cell counts, and infections. However, it can effectively treat CLL.

Overall, these treatments have proven effective and generally safe, but they can have side effects. Always discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining the Bcl-2 inhibitor GDC-0199 with obinutuzumab and ibrutinib for treating Chronic Lymphocytic Leukemia (CLL) because it brings a fresh approach to tackling this cancer. Unlike traditional treatments like chemotherapy, this regimen targets specific pathways within cancer cells. GDC-0199 works by inhibiting the Bcl-2 protein, which helps cancer cells survive, while ibrutinib blocks a different pathway crucial for CLL cell growth. Obinutuzumab, an antibody, directly targets and marks cancer cells for destruction. This combination could potentially result in more effective and less toxic options for CLL patients.

What evidence suggests that this combination treatment could be effective for chronic lymphocytic leukemia?

In this trial, participants will receive a combination of treatments, including the Bcl-2 inhibitor GDC-0199, also known as venetoclax. Research has shown that venetoclax can greatly improve outcomes for patients with chronic lymphocytic leukemia (CLL). Early results indicate that more than 80% of patients respond well to this treatment. Another drug in this trial, ibrutinib, proved very effective, with 96.8% of patients showing a positive response, and many experiencing complete or partial remission. Obinutuzumab, a type of antibody treatment included in this trial, has also been shown to help patients live longer without the disease worsening compared to other treatments. Together, these treatments offer strong potential for effectively managing CLL, especially in difficult-to-treat cases or when the disease returns after initial treatment. ^{1 6 7 8 9}

Who Is on the Research Team?

Kerry Rogers, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Lymphocytic Leukemia (CLL) that's untreated, returned after treatment, or hasn't responded to past treatments. They should be relatively healthy otherwise (ECOG <=1), have adequate kidney function, and not pregnant or able to become pregnant without proper birth control measures. People can't join if they've had certain recent treatments, active infections like HIV or hepatitis B/C, severe allergies to monoclonal antibodies, other cancers within the last 3 years (with some exceptions), or conditions affecting drug absorption.

Inclusion Criteria

Ability to understand and willingness to sign an informed consent document

I am fully active and can carry on all pre-disease activities without restriction.

I have CLL, show symptoms, haven't had chemotherapy, and meet certain lab criteria.

Exclusion Criteria

My cancer has specific mutations or is resistant to some treatments.

I am HIV positive.

My heart condition limits my physical activity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab, ibrutinib, and Bcl-2 inhibitor GDC-0199 in a phased manner over 14 courses

14 months

Monthly visits for each course

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Follow-up at 4 and 8 weeks, every 3 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• GDC-0199
• Ibrutinib
• Obinutuzumab

Trial Overview The trial tests a combination of drugs: GDC-0199 (a Bcl-2 inhibitor), obinutuzumab (a monoclonal antibody), and ibrutinib against CLL. It aims to find the safest doses and see how well these drugs work together in treating CLL by blocking enzymes cancer cells need for growth and targeting specific cells.

How Is the Trial Designed?

Group I: Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) Experimental Treatment 6 Interventions

Patients receive obinutuzumab IV on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib PO QD on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Kerry Rogers

Lead Sponsor

Trials

3

Recruited

120+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39344587/

Efficacy and Effectiveness Outcomes of Treatments for ... ... (BCL2) inhibitor venetoclax have significantly improved outcomes and achieved durable remission in patients with chronic lymphocytic leukemia (CLL). BTKi ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02427451

Study Details | NCT02427451 | Bcl-2 Inhibitor GDC-0199 in ... Giving Bcl-2 inhibitor GDC-0199 together with obinutuzumab and ibrutinib may be a better treatment for chronic lymphocytic leukemia.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.tps7121

A phase 2 open-label study of the efficacy of ABT-199 ... Preliminary phase 1 data with ABT-199 indicate promising therapeutic activity, with a greater than 80% overall response rate in patients (pts) ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/11/2808/536517/Characteristics-and-outcomes-of-patients-with

Characteristics and outcomes of patients with double ... The median OS of patients with DR CLL whose disease progressed during BTK and BCL2 inhibition was 2.2 years. DE CLL represented a less ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8945613/

Outcomes of patients with CLL sequentially resistant to ... Patients with CLL sequentially resistant to both BCL2 and covalent BTK inhibition have a poor prognosis and represent an area of unmet need.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6598635/

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in ... Venetoclax (ABT-199/GDC-0199) is a highly selective bioavailable inhibitor of BCL-2 protein, which is more effective and less valid against BCL- ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.7015

ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic ... ABT-199 induces a high rate of response in pts with R/R CLL, including those with del(17p) and F-refractory disease. Responses are durable.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118474733

Safety and Efficacy of a Combination of Venetoclax (GDC ... These preliminary data suggest that VEN + G can be safely administered in pts with CLL with no difference in tolerability between R/R and TN subgroups. AEs ...

9. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M14-032

A Phase 2 Open-Label Study of the Efficacy and Safety ... This was an open-label, non-randomized, multicenter, Phase 2 study evaluating the efficacy and safety of ABT-199 in 127 participants with relapsed or refractory ...