Venetoclax + Obinutuzumab + Epcoritamab for Chronic Lymphocytic Leukemia

Not yet recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Live vaccines

Disqualifiers: Richter's transformation, CNS involvement, PML, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 30

Duration: 12 cycles (approximately 48 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs to treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in individuals who haven't received prior treatment. It combines venetoclax and obinutuzumab, known for their effectiveness, with a new drug called epcoritamab, an experimental treatment. The aim is to determine if adding epcoritamab can enhance cancer treatment effectiveness and duration. Individuals with CLL or SLL who experience active symptoms, such as extreme fatigue or significant weight loss, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from potentially effective new therapies.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that chronic use of corticosteroids above a certain dose is not allowed, and certain conditions related to anticoagulants and infections are considered. It's best to discuss your specific medications with the trial team.

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

Research shows that using venetoclax and obinutuzumab together is a common treatment for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Studies have found this combination to be safe and effective. Early findings suggest that adding epcoritamab to these two is well-tolerated.

Regarding side effects, venetoclax and obinutuzumab are generally well-tolerated, though patients might experience mild to moderate issues like low blood cell counts or infections, which can be managed. Epcoritamab, being newer, may cause injection site reactions and flu-like symptoms, which are typical for these treatments.

Overall, this combination treatment is designed to be safe. However, like any treatment, some side effects may occur. It's important to discuss expectations with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of venetoclax, obinutuzumab, and epcoritamab for treating Chronic Lymphocytic Leukemia (CLL) because it introduces a novel multi-pronged approach. Unlike traditional treatments like BTK inhibitors or chemoimmunotherapy, this regimen uses venetoclax to induce cancer cell death by targeting the BCL-2 protein, obinutuzumab to enhance the immune system's attack on cancer cells, and epcoritamab, a bispecific antibody that further stimulates immune cells to recognize and destroy cancer. This combination could potentially offer a more comprehensive attack on CLL cells, leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that combining venetoclax and obinutuzumab effectively treats chronic lymphocytic leukemia (CLL). One study found that this combination helped more than half of the patients live for six years without their cancer worsening. Obinutuzumab targets and attacks cancer cells, while venetoclax blocks a protein that helps cancer cells survive. In this trial, participants will receive venetoclax, obinutuzumab, and epcoritamab. Adding epcoritamab, which aids the immune system in attacking cancer, might enhance the treatment's effectiveness and duration. Research supports these treatments, suggesting they offer a promising option for people with untreated CLL. ^{6 7 8 9 10}

Who Is on the Research Team?

Alexey V Danilov

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Participants should not have had previous treatments for these conditions. Specific eligibility criteria are not provided, but typically include factors like age, overall health status, and the stage of cancer.

Inclusion Criteria

If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

My blood clotting time is within the target range for my anticoagulant therapy.

Women of childbearing potential (WOCBP): Negative serum pregnancy test

Exclusion Criteria

Known positive test result for chronic hepatitis B virus (HBV) infection (defined by hepatitis B virus surface antigen [HBsAg] positivity)

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive obinutuzumab, venetoclax, and epcoritamab over 12 cycles, each lasting 28 days

12 cycles (approximately 48 weeks)

Multiple visits per cycle for drug administration and monitoring

Extension

Participants who are MRD positive and have CR, PR, or SD continue receiving epcoritamab for 6 additional cycles

6 cycles (approximately 24 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

Follow-up visits at 30 and 60 days, then every 6 months, and annually after disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Obinutuzumab
• Venetoclax

Trial Overview The LonGEVity trial is testing a combination of venetoclax and obinutuzumab followed by epcoritamab in patients with CLL/SLL. Venetoclax targets proteins that cancer cells need to survive, while obinutuzumab and epcoritamab are antibodies designed to help the immune system attack cancer cells.

How Is the Trial Designed?

Group I: Treatment (obinutuzumab, venetoclax, epcoritamab) Experimental Treatment 9 Interventions

Patients receive obinutuzumab IV on days 1, 2, 8 and 15 of cycle 1 and on day 1 of cycles 2-6, venetoclax PO QD on days 22-28 of cycle 1 and on days 1-28 of cycles thereafter, as well as epcoritamab SC on days 1, 8, 15, and 22 of cycles 7-9 and on day 1 of cycles thereafter. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of 12 cycles, patients who are MRD positive and have CR, PR, or SD continue receiving epcoritamab SC on day 1 of each cycle. Cycles of epcoritamab repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. All patients also undergo blood sample collection and CT or MRI throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/18/1924/516941/Venetoclax-obinutuzumab-for-previously-untreated

6-year results of the randomized phase 3 CLL14 study | Blood One-year fixed-duration Ven-Obi results in durable treatment-free remissions, with a 6-year PFS rate of 53% and TTNT rate of 65%, in CLL. End-of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11551846/

6-year results of the randomized phase 3 CLL14 study One-year fixed-duration Ven-Obi results in durable treatment-free remissions, with a 6-year PFS rate of 53% and TTNT rate of 65%, in CLL.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213093

First-Line Venetoclax Combinations in Chronic ... Dose reductions greater than 20% with any of the agents were performed at least once during treatment in 14.8% of the patients in the ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2025.2535693?af=R

Venetoclax and obinutuzumab in first-line treatment of unfit ... The treatment was effective, with ORR of 97.4%, including 32.7% of CRs and a 2-year PFS of 88.4%. However, nearly 20% of the analyzed patients could not ...

5. venclextahcp.com venclextahcp.com/cll/efficacy/ven-g/data.html

VENCLEXTA efficacy results: 6-year overall survival 1 Learn about VENCLEXTA® 6-year overall survival and treatment efficacy results. See full safety and Prescribing Information for more details.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07218510

Venetoclax and Obinutuzumab Followed by Epcoritamab ... The combination of venetoclax and obinutuzumab is a standard treatment for CLL/SLL and has been found to be safe and effective. Adding ...

7. ashpublications.org ashpublications.org/blood/article/146/2/145/536677/Doubling-down-the-new-deal-in-the-clinical

the new deal in the clinical management of double-refractory ... Once double-refractory disease occurs, prognosis is poor, with median overall survival (OS) of 2.2 years and an estimated 3-year OS rate of 29% ...

8. hematologyadvisor.com hematologyadvisor.com/indepth/chronic-leukemia-icml-2025-progress-future-directions-treatment-risk/

ICML 2025: Progress and Future Directions in CLL Treatment This research included results on retreatment with venetoclax plus obinutuzumab in patients with recurrent CLL, updated results on epcoritamab use in relapsed ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11803567/

Chronic Lymphocytic Leukemia: 2025 Update on the ... The 3‐year overall survival (OS) rates by CLL‐IPI risk groups were 100%, 96%, 93.9%, and 89.4%, respectively, with no differences between consecutive risk ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70064

Advances in the Management of Relapsed/Refractory CLL ... For RT, venetoclax-based chemoimmunotherapy combinations may increase rates of complete response, but remain inadequate for many, highlighting ...