EVOLVE CLL/SLL Study: Early Treatment for High-Risk CLL/SLL
This study, called EVOLVE CLL/SLL, is testing whether starting treatment early with venetoclax and obinutuzumab improves survival for people with newly diagnosed, high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Venetoclax works by blocking a protein (BCL-2) that helps cancer cells survive. Obinutuzumab is an immunotherapy that helps your immune system fight the cancer. You might be able to join if you are 18 or older, have a confirmed diagnosis of CLL or SLL within the last 18 months, and have a high-risk score (CLL-IPI score of 4 or higher). The study aims to see if early treatment leads to better overall survival, measured up to 10 years, and also looks at your quality of life.
- Study design
- This interventional study plans to enroll 247 participants to compare early treatment versus delayed treatment with venetoclax and obinutuzumab.
- What's involved
- You would undergo blood sample collection, bone marrow aspiration, bone marrow biopsy, CT scans, and receive obinutuzumab intravenously.
- Compensation
- Not stated in the trial record.
- Follow-up
- Overall survival will be measured for up to 10 years, and quality of life will be assessed at 2 years.
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NCT04269902
Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study
Recruiting
PHASE3Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~247 participants
Updated 2026-08-27 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyObinutuzumabQuestionnaire Administration
At a glance
Recruiting sites
302 of 631 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall survival (OS)
Measured over From the day of registration on study until death from any cause with observations censored on the day of last contact for participants not known to have died, assessed up to 10 years
+1 more outcome measured
Conditions
Where it's being run
631 sites across 50 statesMichigan69
Ohio66
Illinois58
California43
Colorado42
Washington33
Minnesota32
Missouri31
Study leadership
- Deborah M Stephens · PRINCIPAL_INVESTIGATOR · SWOG Cancer Research Network
Who to contact
Site Public Contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration
Participants must have CLL-International Prognostic Index (CLL-IPI) score \>= 4 and/or complex cytogenetics (defined as 3+ chromosomal abnormalities)
Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p
TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p)
Note: TP53 gene mutation analysis is recommended but not required if the participant meets disease-related study criteria via a combination of risk factors that totals a score of 4 on the CLL-IPI score and/or has complex cytogenetics completed
Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis performed at any CLIA-approved lab (or laboratories accredited under Accreditation Canada Diagnostics) must be obtained prior to registration (at any time prior to registration)
Serum beta-2 microglobulin level must be obtained within 28 days prior to registration
Participants must not meet any of the IWCLL specified criteria for active CLL therapy
Treatment with high dose corticosteroids and/or intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment
Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
Prior therapy with anti CD20 monoclonal antibodies is not allowed
Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of coronavirus disease 2019 \[COVID-19\]), or radiotherapy
Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy
Participants must be \>= 18 years of age
Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
Platelet count \>= 100,000/mm\^3 within 28 days prior to registration
Absolute neutrophil count (ANC) \>= 1,000/mm\^3 within 28 days prior to registration
Creatinine clearance \>= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x upper limit of normal (ULN) within 28 days prior to registration
Total bilirubin =\< 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert's disease), within 28 days prior to registration
Participants must be able to take oral medications
Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Participants with history of malignancy are allowed providing the cancer has not required active treatment within 2 years prior to registration (hormonal therapy is permissible). The following exceptions are permissible: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer treated with surgical resection and/or radiation only or requiring no more than chronic hormonal therapy, or prostate cancer with Gleason score ≤ 6, or localized breast cancer treated with surgical resection and/or radiation only or requiring no more than chronic hormonal therapy
Participants must not have current, clinically significant gastrointestinal malabsorption, in the opinion of treating doctor
Participants must not have cirrhosis
Obinutuzumab has been associated with hepatitis reactivation. Participants must not have uncontrolled active infection with hepatitis B or C. Participants with latent hepatitis B infection must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O.
Active infection with hepatitis B or C:
Active infection is defined as detectable hepatitis B deoxyribonucleic acid (DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain reaction (PCR).
Latent infection with hepatitis B:
Latent infection is defined as meeting all of the following criteria:
Hepatitis B surface antigen positive
Anti-hepatitis B total core antibody positive
Anti-hepatitis IgM core antibody undetectable
Hepatitis B PCR undetectable
Participants with latent hepatitis B infection must agree to take prophylaxis with anti-hepatitis agents during and for 6 months following active protocol therapy with V-O.
Participants who have received intravenous immunoglobulin (IVIG) therapy within 6 months who are hepatitis B core total antibody positive but PCR undetectable are not mandated to take prophylaxis
Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration. Examples of major surgery include neurosurgical procedures, joint replacements, and surgeries that occur inside the thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this will not exclude the participant from registration to the study. If there is a question about whether a surgery is major or minor, this should be discussed with the Study Chair
Participants must not have known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment
Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5
Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification
Participants must not have a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
Participants must not be pregnant or nursing, as there are no safety data available for these drug regimens during pregnancy. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Participants must agree to have specimens submitted for translational medicine (MRD) as outlined
Participants must be offered the opportunity to participate in specimen banking for future research as outlined.
NOTE: With participant's consent, the site must follow through with specimen submission as outlined
Participants who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must be offered the opportunity to participate in the quality of life assessments. (Those participants who are unable to read and write in English, Spanish, French, German, Russian or Mandarin may be registered to S1925 without contributing to the quality of life portion of the study.)
Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
What this trial measures
- Overall survival (OS)From the day of registration on study until death from any cause with observations censored on the day of last contact for participants not known to have died, assessed up to 10 years
The final analysis will use stratified Cox proportional hazards regression stratified by Chronic Lymphocytic Leukemia \[CLL\] International Prognostic Indicator Risk score status (high risk versus very high risk) with a two-sided alpha of 0.05. The final analysis will occur after 58 OS events have been observed, or at 4 years after accrual completes, whichever occurs first. Under the alternative hypothesis, the final analysis is expected to occur at approximately 7.9 years after study activation (about 3.8 years after accrual completes).
- Functional Assessment of Cancer Therapy (FACT)-Leukemia total scoreAt 2 years
A single comparison in the FACT-Leukemia total scores between patients randomized to early V-O versus delayed V-O will be conducted at the alpha=.05 level. The analysis of the 2-year FACT-Leukemia Total score will be conducted using multiple linear regression analysis, adjusting for stratification factor and the baseline FACT-Leukemia Total score as covariates. Will also conduct longitudinal modeling of the outcome measures over time.