Clinical trial Recruiting at 299 sites Phase 3 Interventional Ages 18 and up

Early treatment for high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma

Official title: Randomized, Phase III Study of Early Intervention With Venetoclax and Obinutuzumab Versus Delayed Therapy With Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): EVOLVE CLL/SLL Study

Run by National Cancer Institute (NCI) · NCT04269902 · Data updated 2026-11-12

This study tests if starting treatment early with venetoclax and obinutuzumab can help people newly diagnosed with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma live longer and feel better compared to waiting until symptoms show up.

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment247 (estimated)
SponsorNational Cancer Institute (NCI)
NIH
Drugs / interventionsObinutuzumab, chemotherapy, immunotherapy, radiation, prednisone
Locations633 sites (Birmingham, Alabama and 632 other locations)
StatusRecruiting
StartedMarch 2, 2021
Main results expectedOctober 1, 2028
Study endsOctober 1, 2028
Registry record updatedNovember 5, 2026
Trial IDNCT04269902 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are individuals diagnosed with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma within the last 18 months.

Probably not a fit

Patients with low-risk CLL or SLL or those who have already received treatment may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase III trial compares the effects of early treatment using venetoclax and obinutuzumab against delayed treatment in patients newly diagnosed with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study aims to determine if starting treatment before symptoms appear can improve overall survival and other clinical outcomes. Participants will be monitored for response rates, progression-free survival, and safety of the treatment. The trial also evaluates the impact of treatment timing on patients' quality of life.

Why it matters

Potential benefit: If successful, this approach could lead to improved survival rates and better quality of life for patients with high-risk CLL or SLL.

How similar studies have gone: Other studies have shown promising results with early treatment approaches in similar patient populations, suggesting potential for success.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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

Where it's running

  • Banner University Medical Center - Tucson
    Tucson, Arizona, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona, United States
    Recruiting
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas, United States
    Recruiting
  • Kaiser Permanente-Anaheim
    Anaheim, California, United States
    Recruiting
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California, United States
    Recruiting
  • Kaiser Permanente-Bellflower
    Bellflower, California, United States
    Recruiting
Show 44 more locations
  • Marshall Cancer Center
    Cameron Park, California, United States
    Recruiting
  • Enloe Medical Center
    Chico, California, United States
    Recruiting
  • UC Irvine Health Cancer Center-Newport
    Costa Mesa, California, United States
    Recruiting
  • City of Hope Comprehensive Cancer Center
    Duarte, California, United States
    Recruiting
  • Kaiser Permanente-Fontana
    Fontana, California, United States
    Recruiting
  • Kaiser Permanente South Bay
    Harbor City, California, United States
    Recruiting
  • City of Hope Seacliff
    Huntington Beach, California, United States
    Recruiting
  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
    Irvine, California, United States
    Recruiting
  • City of Hope at Irvine Lennar
    Irvine, California, United States
    Recruiting
  • Kaiser Permanente-Irvine
    Irvine, California, United States
    Recruiting
  • UCI Health Laguna Hills
    Laguna Hills, California, United States
    Recruiting
  • City of Hope Antelope Valley
    Lancaster, California, United States
    Recruiting
  • City of Hope at Long Beach Elm
    Long Beach, California, United States
    Recruiting
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, United States
    Recruiting
  • Kaiser Permanente West Los Angeles
    Los Angeles, California, United States
    Recruiting
  • Fremont - Rideout Cancer Center
    Marysville, California, United States
    Recruiting
  • City of Hope Newport Beach
    Newport Beach, California, United States
    Recruiting
  • Kaiser Permanente-Ontario
    Ontario, California, United States
    Recruiting
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, United States
    Recruiting
  • Kaiser Permanente - Panorama City
    Panorama City, California, United States
    Recruiting
  • Kaiser Permanente-Riverside
    Riverside, California, United States
    Recruiting
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, United States
    Recruiting
  • Kaiser Permanente-San Diego Zion
    San Diego, California, United States
    Recruiting
  • Kaiser Permanente-San Marcos
    San Marcos, California, United States
    Recruiting
  • City of Hope South Pasadena
    South Pasadena, California, United States
    Recruiting
  • City of Hope South Bay
    Torrance, California, United States
    Recruiting
  • City of Hope Upland
    Upland, California, United States
    Recruiting
  • Kaiser Permanente-Woodland Hills
    Woodland Hills, California, United States
    Recruiting
  • Grand Valley Oncology
    Grand Junction, Colorado, United States
    Recruiting
  • Beebe South Coastal Health Campus
    Millville, Delaware, United States
    Recruiting
  • Helen F Graham Cancer Center
    Newark, Delaware, United States
    Recruiting
  • Medical Oncology Hematology Consultants PA
    Newark, Delaware, United States
    Recruiting
  • Beebe Health Campus
    Rehoboth Beach, Delaware, United States
    Recruiting
  • Sibley Memorial Hospital
    Washington D.C., District of Columbia, United States
    Recruiting
  • Holy Cross Hospital
    Fort Lauderdale, Florida, United States
    Recruiting
  • Saint Alphonsus Cancer Care Center-Boise
    Boise, Idaho, United States
    Recruiting
  • Saint Alphonsus Cancer Care Center-Caldwell
    Caldwell, Idaho, United States
    Recruiting
  • Kootenai Health - Coeur d'Alene
    Coeur d'Alene, Idaho, United States
    Recruiting
  • Saint Alphonsus Cancer Care Center-Nampa
    Nampa, Idaho, United States
    Recruiting
  • Kootenai Clinic Cancer Services - Post Falls
    Post Falls, Idaho, United States
    Recruiting
  • Kootenai Clinic Cancer Services - Sandpoint
    Sandpoint, Idaho, United States
    Recruiting
  • Northwestern University
    Chicago, Illinois, United States
    Recruiting
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois, United States
    Recruiting
  • Carle at The Riverfront
    Danville, Illinois, United States
    Recruiting

+583 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Deborah M Stephens — SWOG Cancer Research Network

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.