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

Actively Recruiting

Phase 3

Age: 18Years +

All Genders

NCT04269902

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

Led by National Cancer Institute (NCI) · Updated on 2026-05-14

247

Participants Needed

629

Research Sites

395 weeks

Total Duration

AI-Summary

What this Trial Is About

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. 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. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

CONDITIONS

Official 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...

Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) within 18 months prior to registration
CLL-International Prognostic Index (CLL-IPI) score of 4 or higher and/or complex cytogenetics (3 or more chromosomal abnormalities)
Cytogenetic and/or FISH analyses completed at an accredited laboratory within 18 months prior to registration
TP53 gene mutation analysis performed within 18 months prior to registration if available
Immunoglobulin heavy chain variable region (IgVH) gene mutation analysis completed prior to registration
Serum beta-2 microglobulin level obtained within 28 days prior to registration
No active CLL therapy criteria met according to IWCLL guidelines
Completed treatment with high dose corticosteroids or intravenous immunoglobulin for autoimmune complications at least 4 weeks before enrollment
Steroid dose for other conditions at 20 mg/day prednisone or less at registration
No prior anti-CD20 monoclonal antibody therapy
No previous or current CLL-directed therapy, immunotherapy, experimental therapy (except emergency COVID-19 agents), or radiotherapy
Not receiving or planning other investigational agents before completing protocol therapy
Age 18 years or older
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Platelet count of 100,000/mm3 or higher within 28 days prior to registration
Absolute neutrophil count (ANC) of 1,000/mm3 or higher within 28 days prior to registration
Creatinine clearance 30 mL/min or higher within 28 days prior to registration
AST and ALT less than 3 times upper limit of normal within 28 days prior to registration
Total bilirubin 2 times upper limit of normal or less (or 5 times if history of Gilbert's disease) within 28 days prior to registration
Able to take oral medications
HIV-infected participants on effective antiretroviral therapy with undetectable viral load within 6 months eligible
History of malignancy allowed if no active treatment within 2 years except certain skin, cervical, bladder, prostate, or breast cancers
No clinically significant gastrointestinal malabsorption
No cirrhosis
No uncontrolled active hepatitis B or C infection; latent hepatitis B infection participants must agree to prophylaxis
No major surgery within 30 days or minor surgery within 7 days prior to registration (except bone marrow biopsy)
No known bleeding disorders
No history of stroke or intracranial hemorrhage within 6 months prior to enrollment
No need for continued strong CYP3A4/5 inhibitor or inducer therapy
No uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
No active significant cardiovascular disease such as uncontrolled arrhythmia or severe heart failure
No myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
Not pregnant or nursing; agreement to use effective contraception if of reproductive potential
Agree to specimen submission for translational medicine and optional specimen banking
Able and willing to complete quality of life assessments in English, Spanish, French, German, Russian or Mandarin
Provide informed consent according to guidelines

You will not qualify if you...

Prior therapy with anti-CD20 monoclonal antibodies
Previous or current CLL-directed therapy, including immunotherapy, experimental therapy (except emergency COVID-19 agents), or radiotherapy
Meeting IWCLL criteria for active CLL therapy at registration
Receiving or planning to receive other investigational agents before completing protocol therapy
Clinically significant gastrointestinal malabsorption
Cirrhosis
Uncontrolled active infection with hepatitis B or C
Major surgery within 30 days or minor surgery within 7 days prior to registration (except bone marrow biopsy)
Known bleeding disorders such as von Willebrand's disease or hemophilia
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Need for continuing therapy with strong CYP3A4/5 inhibitors or inducers
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
Active, clinically significant cardiovascular disease including uncontrolled arrhythmia or advanced congestive heart failure
History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
Pregnant or nursing women
Unable or unwilling to use effective contraception if of reproductive potential

AI-Screening

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Trial Site Locations

Total: 629 locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States, 35233

Active, Not Recruiting

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, United States, 98508

Suspended

Anchorage Radiation Therapy Center

Anchorage, Alaska, United States, 99504

Suspended

Alaska Breast Care and Surgery LLC