Chronic Lymphocytic LeukemiaPhase 2NCT07218510
Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, LonGEVity Trial
A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Jan 2026to 8 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Histologically confirmed or flow cytometry confirmed diagnosis of B-CLL/SLL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO)
- No prior treatment for CLL/SLL, except steroids and/or rituximab to treat autoimmune complications
Show all 41Show fewer
- Evidence of CD20 positivity
- Active disease meeting criteria for requiring treatment per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines
- A minimum of any one of the following constitutional symptoms:
- Unintentional weight loss > 10% within the previous 6 months prior to screening
- Extreme fatigue (unable to work or perform usual activities)
- Fevers of greater than 100.5°F for ≥ 2 weeks without evidence of infection
- Night sweats without evidence of infection
- Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia
- Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly
- Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy
- Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months
- Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
- Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine)
- Participant must be able to swallow tablets or capsules. A participant with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible
- Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement.
- With bone marrow involvement: ANC ≥ 500/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement.
- Without bone marrow involvement: Platelets ≥ 50,000/mm^3
- NOTE: independent of transfusion support, with no active bleeding
- With bone marrow involvement: Platelets ≥ 30,000/mm^3
- NOTE: independent of transfusion support, with no active bleeding
- Direct bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease or compensated hemolysis directly attributable to CLL)
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Estimated creatinine clearance of ≥ 40 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 formula
- If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
- If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
- If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
- If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
- Women of childbearing potential (WOCBP): Negative serum pregnancy test
- Agreement by females of childbearing potential to either abstain from heterosexual activity or use an effective method of birth control (failure rate of < 1% per year) during the treatment period and through at least 30 days after the last dose of venetoclax, 18 months after the last dose of obinutuzumab, 12 months after the last dose of epcoritamab, and at least 4 months after the last dose of tocilizumab (if applicable). Women must refrain from donating eggs during this same period
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
- Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices
- Agreement by males to either abstain from heterosexual activity or use a condom during the treatment period and through at least 30 days after the last dose of venetoclax, 4 months after the last dose of obinutuzumab, epcoritamab or tocilizumab (as applicable). Men with a pregnant partner must agree to remain abstinent or use a condom for the duration of the pregnancy. Men must refrain from donating sperm during this same period
Who cannot join
- Chronic use of corticosteroids in excess of 20 mg/day prednisone or equivalent
- Major surgery (under general anesthesia) within 30 days prior to cycle 1 day 1 (C1D1)
- Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are allowed
- Exposure to vaccination with live vaccine within 30 days prior to C1D1, or anticipated need for such vaccination during treatment
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation)
- Current evidence of central nervous system involvement by the CLL
Show all 23Show fewer
- History of confirmed progressive multifocal leukoencephalopathy (PML)
- History of prior malignancy except:
- Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study
- Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
- Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease
- Asymptomatic prostate cancer managed with "watch and wait" strategy
- Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
- Uncontrolled active systemic infection
- Known positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing) and a positive test result for HCV ribonucleic acid (RNA). Participants with positive serology are eligible in case of negative HCV RNA test results
- Known positive test result for chronic hepatitis B virus (HBV) infection (defined by hepatitis B virus surface antigen [HBsAg] positivity)
- Participants with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody) may be included if HBV deoxyribonucleic acid (DNA) is undetectable, provided that they are willing to undergo ongoing DNA testing
- Antiviral prophylaxis may be administered as per institutional guidelines
- Participants who have protective titers of hepatitis B virus surface antibody (HBsAb) after vaccination or prior but cured hepatitis B may be included if HBV DNA is undetectable
- Participants with HIV may be enrolled if they are on concurrent highly active antiretroviral therapy (HAART) therapy, have undetectable HIV RNA levels and no evidence of HIV-related comorbidities (infections or malignancies), and provided that they meet all other protocol-defined eligibility criteria
- Females only: Pregnant or breastfeeding
- 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)
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Alexey V. Danilov, 626-218-2405, adanilov@coh.org
Alexey V. Danilov
- Recruiting
City of Hope at Irvine Lennar
Irvine, California, 92618
Alexey V. Danilov, 626-218-2405, adanilov@coh.org
Alexey V. Danilov
- Recruiting
City of Hope at Long Beach Elm
Long Beach, California, 90813
Alexey V. Danilov, 626-218-2405, adanilov@coh.org
Alexey V. Danilov
- Not yet recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Georgios Pongas, gpongas@med.miami.edu
Georgios Pongas
- Not yet recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Guru Subramanian Guru Murthy, gmurthy@mcw.edu
Guru Subramanian Guru Murthy
- Not yet recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
John P. Leonard, John.Leonard@nyulangone.org
John P. Leonard
- Recruiting
City of Hope Atlanta Cancer Center
Newnan, Georgia, 30265
Alexey V. Danilov, 626-218-2405, adanilov@coh.org
Alexey V. Danilov
About this study
Official title: A Phase 2 Study of Venetoclax + Obinutuzumab Followed by Epcoritamab in Previously Untreated Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (LonGEVity)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Being tested
- Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Electronic Health Record Review
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration and biopsy
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow aspiration and biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Electronic Health Record ReviewOther
Ancillary studies
EpcoritamabBiological
Also called Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly
Given SC
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
ObinutuzumabBiological
Also called Anti-CD20 Monoclonal Antibody R7159, GA 101, GA-101, GA101
Given IV
VenetoclaxDrug
Also called ABT 199, ABT-0199, ABT-199, ABT199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (obinutuzumab, venetoclax, epcoritamab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Other: Electronic Health Record Review; Biological: Epcoritamab; Procedure: Magnetic Resonance Imaging; Biological: Obinutuzumab; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal residual disease (MRD) negative complete response (CR)
MRD status will be assessed using ClonoSEQ® (Adaptive Biotechnologies™) on the blood (sensitivity at 10^-4 and 10^-6). The determination of MRD status (i.e. positive versus negative) will be defined as the presence or absence of measurable clonotypes, respectively, at a sensitivity of 10^-6. Will be estimated along with the 95% exact binomial confidence interval.
Measured: At beginning of cycle 12 (cycle length = 28 days)
Secondary outcomes (5)
Overall response rate
Will be defined as achieving a best response of either CR or partial response (PR) in a response-evaluable participant. Will be estimated along with the 95% exact binomial confidence interval.
Measured: After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 5 years
Progression-free survival (PFS)
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval for survival at specific timepoints will be constructed based on log-log transformation. Median PFS will be estimated when possible.
Measured: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 5 years
Duration of response (DOR)
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval for survival at specific timepoints will be constructed based on log-log transformation. Median DOR will be estimated when possible.
Measured: From the first achievement of PR or CR to time of disease relapse/progression or death, whichever earlier, assessed up to 5 years
Overall survival (OS)
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval for survival at specific timepoints will be constructed based on log-log transformation. Median OS will be estimated when possible.
Measured: From start of protocol treatment to death due to any cause, assessed up to 5 years
Incidence of adverse events
Will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Hematologic toxicities will be graded according to International Workshop on Chronic Lymphocytic Leukemia. Cytokine release syndrome and immune effector cell associated neurotoxicity syndrome will be graded according to the American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome Consensus Grading criteria. Observed toxicities will be summarized by type, severity, and attribution.
Measured: Up to 60 days after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2025
- Study start7 Jan 2026
- Primary completion8 Jun 2029 (estimated)
- Study completion8 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Alexey V Danilov, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07218510
- Sponsor's protocol ID
- 24230
- Other IDs
- NCI-2025-07205, 24230, P30CA033572
- Status last verified
- Mar 2026
- First submitted
- 16 Oct 2025
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Venetoclax + Obinutuzumab Followed by Epcoritamab in Previously Untreated Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (LonGEVity)
- ClinicalTrials.gov ID
- NCT07218510
- Acronym / sponsor ID
- 24230
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Jan 2026 (actual)
- Primary completion
- 8 Jun 2029 (estimated)
- Study completion
- 8 Jun 2029 (estimated)
- First posted
- 20 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (obinutuzumab, venetoclax, epcoritamab) | Experimental | Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Computed Tomography, Other: Electronic Health Record Review, Biological: Epcoritamab, Procedure: Magnetic Resonance Imaging, Biological: Obinutuzumab, Drug: VenetoclaxPatients 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- Documented informed consent of the participant and/or legally authorized representative
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Histologically confirmed or flow cytometry confirmed diagnosis of B-CLL/SLL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO)
- No prior treatment for CLL/SLL, except steroids and/or rituximab to treat autoimmune complications
Key exclusion criteria (23 listed)
- Chronic use of corticosteroids in excess of 20 mg/day prednisone or equivalent
- Major surgery (under general anesthesia) within 30 days prior to cycle 1 day 1 (C1D1)
- Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are allowed
- Exposure to vaccination with live vaccine within 30 days prior to C1D1, or anticipated need for such vaccination during treatment
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| Bone Marrow AspirationUndergo bone marrow aspiration and biopsy | Procedure or surgery | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo bone marrow aspiration and biopsy | Procedure or surgery | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| Electronic Health Record ReviewAncillary studies | Other | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| EpcoritamabAlso: Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, EpkinlyGiven SC | Biological | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| ObinutuzumabAlso: Anti-CD20 Monoclonal Antibody R7159, GA 101, GA-101, GA101Given IV | Biological | Treatment (obinutuzumab, venetoclax, epcoritamab) |
| VenetoclaxAlso: ABT 199, ABT-0199, ABT-199, ABT199Given PO | Drug | Treatment (obinutuzumab, venetoclax, epcoritamab) |
Primary outcome
Minimal residual disease (MRD) negative complete response (CR)
Time frame: At beginning of cycle 12 (cycle length = 28 days)
MRD status will be assessed using ClonoSEQ® (Adaptive Biotechnologies™) on the blood (sensitivity at 10^-4 and 10^-6). The determination of MRD status (i.e. positive versus negative) will be defined as the presence or absence of measurable clonotypes, respectively, at a sensitivity of 10^-6. Will be estimated along with the 95% exact binomial confidence interval.
5 secondary outcomes
Overall response rate
Time frame: After the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy, assessed up to 5 years
Progression-free survival (PFS)
Time frame: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 5 years
Duration of response (DOR)
Time frame: From the first achievement of PR or CR to time of disease relapse/progression or death, whichever earlier, assessed up to 5 years
Overall survival (OS)
Time frame: From start of protocol treatment to death due to any cause, assessed up to 5 years
Incidence of adverse events
Time frame: Up to 60 days after last dose of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
Related trials for Chronic Lymphocytic Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexey V Danilov principal investigator
City of Hope Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minimal residual disease (MRD) negative complete response (CR) (time frame: At beginning of cycle 12 (cycle length = 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.