NCT07218510

Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, LonGEVity Trial

A Phase 2 Study of Venetoclax + Obinutuzumab Followed by Epcoritamab in Previously Untreated Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (LonGEVity)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests the effect of venetoclax and obinutuzumab followed by epcoritamab in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that have not previously received treatment. 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. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Epcoritamab, a bispecific monoclonal antibody, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. The combination of venetoclax and obinutuzumab is a standard treatment for CLL/SLL and has been found to be safe and effective. Adding epcoritamab to standard treatment with venetoclax and obinutuzumab may lead to deeper and longer-lasting responses in patients with untreated CLL/SLL.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate the efficacy of venetoclax and obinutuzumab followed by venetoclax and epcoritamab in patients with newly diagnosed CLL/SLL, as assessed by the minimal residual disease (MRD)-negative complete response (CR) rate at 12 cycles of therapy. SECONDARY OBJECTIVES: I. Evaluate the safety and tolerability of venetoclax and obinutuzumab followed by venetoclax and epcoritamab in patients with newly diagnosed CLL/SLL. II. Evaluate the overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) in patients with newly diagnosed CLL/SLL who received venetoclax and obinutuzumab followed by venetoclax and epcoritamab. EXPLORATORY OBJECTIVES: I. Examine T cell and natural killer (NK) cell immune function in patients with newly diagnosed CLL/SLL treated with venetoclax and obinutuzumab followed by venetoclax and epcoritamab. II. Examine the association between established biomarkers (chromosomal abnormalities, immunoglobulin heavy chain \[IGHV\] mutational status, TP53 mutational status) and clinical outcomes (ORR, PFS). OUTLINE: Patients receive obinutuzumab intravenously (IV) on days 1, 2, 8 and 15 of cycle 1 and on day 1 of cycles 2-6, venetoclax orally (PO) once daily (QD) on days 22-28 of cycle 1 and on days 1-28 of cycles thereafter, as well as epcoritamab subcutaneously (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, partial response (PR), or stable disease (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 computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy throughout the study. After completion of study treatment, patients are followed up at 30 and 60 days, then every 6 months (for patients who have not experienced disease progression) and 12 months (after disease progression) for up to 5 years.

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Computed Tomography	Undergo CT
OTHER	Electronic Health Record Review	Ancillary studies
BIOLOGICAL	Epcoritamab	Given SC
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Obinutuzumab	Given IV
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2026-01-07
• Primary completion: 2029-06-08
• Completion: 2029-06-08
• First posted: 2025-10-20
• Last updated: 2026-03-13

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study