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

Plain English Summary

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma. This study tests if starting treatment with venetoclax and obinutuzumab earlier, before symptoms appear, is better than waiting until symptoms develop for patients with high-risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). It is for newly diagnosed adults with high-risk CLL/SLL who do not yet have symptoms requiring immediate treatment. Participation involves receiving either early or delayed treatment with venetoclax and obinutuzumab, along with regular medical check-ups, blood tests, and potentially bone marrow biopsies. Alternative treatments for CLL/SLL include watchful waiting (if asymptomatic and low-risk), chemotherapy, targeted therapies, and stem cell transplant, depending on the individual's condition and risk factors. The trial aims to enroll 247 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of CLL/SLL made within the last 18 months. Patients must have specific high-risk indicators, such as a high score on the CLL-IPI risk assessment or multiple genetic abnormalities. Individuals must not have received prior treatment for CLL/SLL, including certain other cancer therapies or high-dose steroids. Participants should have generally good health, with adequate blood counts, kidney, and liver function, and be able to take oral medications. This trial is studying Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how long patients live overall and their quality of life as assessed by a leukemia-specific questionnaire, indicating the treatment's impact on survival and well-being. The specific primary outcome measures are: 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); Functional Assessment of Cancer Therapy (FACT)-Leukemia total score (At 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a gap in understanding the optimal timing of treatment for high-risk CLL/SLL, aiming to improve outcomes by investigating if early intervention with novel agents can prevent disea As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, where improved treatment options are needed.

Investor Insight

This Phase III trial, sponsored by the National Cancer Institute, investigates a combination therapy for a significant patient population, suggesting potential for a new standard of care if early inte Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of venetoclax and obinutuzumab, and what 'early' versus 'delayed' treatment means for your situation. Be prepared for regular clinic visits for infusions, blood draws, and monitoring. The study is expected to last up to 10 years for follow-up. You may need to undergo procedures like bone marrow aspiration or biopsy, and CT scans as part of the study. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 247 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• PROCEDURE: Bone Marrow Aspiration — Undergo bone marrow aspiration
• PROCEDURE: Bone Marrow Biopsy — Undergo bone marrow biopsy
• PROCEDURE: Computed Tomography — Undergo CT
• BIOLOGICAL: Obinutuzumab — Given IV

Primary Outcomes

• 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)
• Functional Assessment of Cancer Therapy (FACT)-Leukemia total score (At 2 years)

Secondary Outcomes

• Incidence of adverse events (Up to 10 years)
• Overall Response rate (Up to 10 years)
• Progression free survival (From the day of registration on study until the first of: relapse from complete response, progression, or death from any cause, assessed up to 10 years)
• Event free survival (From the day of registration on study until the first of: relapse from complete response, death from any cause, start of new (non-protocol) therapy, or completion of protocol therapy without documentation of complete response, assessed up to 10 years)
• Relapse free survival (From the date the participant first achieves complete response until relapse from complete response or death from any cause, assessed up to 10 years)

Full Eligibility 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 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 requiring no more than chronic hormonal therapy, or localized breast cancer 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

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• B-cell Lymphoma
• Hematologic Malignancies
• Leukemia
• Lymphoma
• Non-Hodgkin Lymphoma
• Myelodysplastic Syndromes
• Bone Marrow Neoplasms
• Plasma Cell Dyscrasias

More Chronic Lymphocytic Leukemia Trials

View all Chronic Lymphocytic Leukemia clinical trials