What is venetoclax and obinutuzumab studying for high-risk chronic lymphocytic leukemia and small lymphocytic lymphoma?

This trial is studying whether starting treatment early with venetoclax and obinutuzumab improves survival compared to waiting until symptoms appear in high-risk patients with CLL or SLL. Researchers aim to understand if early intervention offers better disease control and quality of life. The study is sponsored by the National Cancer Institute (NCI).

Who may be eligible for this high-risk chronic lymphocytic leukemia clinical trial?

Adults aged 18 years and older with a recent diagnosis of high-risk CLL or SLL may be eligible. Participants must not have received prior CLL-directed therapy and should have good overall health with specific blood counts and organ function. Please review eligibility criteria for more details.

Is there any cost to participate in this high-risk chronic lymphocytic leukemia clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal travel and related expenses may vary and might not be covered. Participants should consider their own costs when deciding about participation.

Actively Recruiting

Phase 3

Age: 18Years +

All Genders

ID04269902

Phase III Study Comparing Early Versus Delayed Treatment With Venetoclax and Obinutuzumab in Newly Diagnosed High-Risk Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Led by National Cancer Institute (NCI) · Updated on 2026-08-07

247

Participants Needed

631

Research Sites

N/A

Total Duration

AI-Summary

What this Trial Is About

Researchers are evaluating early versus delayed treatment with venetoclax and obinutuzumab in patients newly diagnosed with high-risk chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. This phase III trial aims to determine if starting treatment before symptoms appear improves overall survival and other outcomes compared to starting treatment after symptoms develop. Venetoclax blocks a protein important for cancer cell survival, while obinutuzumab is an immunotherapy antibody that may help the immune system attack cancer cells. Participants are randomly assigned to receive either early or delayed treatment with venetoclax and obinutuzumab. Both groups receive obinutuzumab intravenously on specific days during six cycles and venetoclax orally daily for up to 12 cycles, each cycle lasting 28 days. Treatment continues unless disease progression or unacceptable side effects occur. During and after treatment, patients undergo CT scans, blood sample collection, and bone marrow biopsies. Throughout the study, participants are closely monitored with various assessments including laboratory tests, imaging, and quality of life questionnaires. Researchers measure overall survival, response rates, progression-free survival, and patient-reported outcomes over up to 10 years. Safety, tolerability, and disease markers such as measurable residual disease are also evaluated. Follow-up continues for 10 years after treatment completion to observe long-term outcomes.

CONDITIONS

Brief Title

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Adults 18 years or older
Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) within 18 months prior to registration
High-risk disease defined by CLL-International Prognostic Index (CLL-IPI) score 6 4 or complex cytogenetics (3 or more chromosomal abnormalities)
Cytogenetic and/or FISH analyses completed within 18 months prior to registration
TP53 gene mutation analysis obtained if performed within 18 months prior to registration
Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis obtained prior to registration
Serum beta-2 microglobulin level obtained within 28 days prior to registration
No active CLL therapy indications based on 2018 IWCLL criteria
Completed high-dose corticosteroids or intravenous immunoglobulin for CLL complications at least 4 weeks prior
Steroid treatment for other conditions limited to 20 mg/day prednisone or equivalent at registration
No prior anti-CD20 monoclonal antibody therapy
No previous CLL-directed therapy
Not receiving or planning other investigational agents before completing protocol therapy
Eastern Cooperative Oncology Group (ECOG) performance status 4
Platelet count 100,000/mm3 within 28 days prior to registration
Absolute neutrophil count (ANC) 1,000/mm3 within 28 days prior to registration
Creatinine clearance 30 mL/min within 28 days prior to registration
AST and ALT levels less than 3 times upper limit of normal within 28 days prior to registration
Total bilirubin 2 times upper limit of normal (or 5 if history of Gilbert's disease) within 28 days prior to registration
Able to take oral medications
HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months
History of malignancy allowed if no active treatment required within 2 years prior
No clinically significant gastrointestinal malabsorption
No cirrhosis
No uncontrolled active hepatitis B or C infection; latent hepatitis B infection participants must take prophylaxis during and 6 months after treatment
No major surgery within 30 days or minor surgery within 7 days prior to registration
No known bleeding disorders
No history of stroke or intracranial hemorrhage within 6 months prior to enrollment
Not requiring strong CYP3A4/5 inhibitors or inducers
No uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
No active clinically significant cardiovascular disease
No myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior
Not pregnant or nursing; effective contraception required for reproductive potential
Agree to translational medicine specimen submission
Offered participation in specimen banking and quality of life assessments
Informed consent obtained according to guidelines

You will not qualify if you...

Prior therapy with anti-CD20 monoclonal antibodies
Received or currently receiving any prior CLL-directed therapy including chemotherapy or experimental agents
Active infection with hepatitis B or C
Major surgery within 30 days or minor surgery within 7 days prior to registration
Known bleeding disorders such as von Willebrand's disease or hemophilia
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Requirement for strong CYP3A4/5 inhibitors or inducers
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
Active clinically significant cardiovascular disease, including uncontrolled arrhythmia or severe heart failure
History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
Pregnancy or nursing
Clinically significant gastrointestinal malabsorption
Cirrhosis
Uncontrolled active infection with hepatitis B or C
Participants who do not agree to contraceptive measures if of reproductive potential
Participants unable to provide informed consent

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Phase III Study Comparing Early Versus Delayed Treatment With Venetoclax and Obinutuzumab in Newly Diagnosed High-Risk Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

On this page

AI-Summary

What this Trial Is About

Brief Title

Who Can Participate

Eligibility Criteria

Not the Right Trial for You?

On this page

Who Can Participate

Eligibility Criteria