NCT04269902|RecruitingPhase 3FDA Drug

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

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2020-00752S1925U10CA180888

Study Type

interventional

Target

247

Locations

2 countries

Sites

629

Timeline

RegisteredFeb 2020

StartedMar 2021

CompletionOct 2028

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

247

participants targeted

Target at P50-P75 for phase_3

Timeline

29mo left

Started Mar 2021

Longer than P75 for phase_3

Geographic Reach

2 countries

629 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.6 years study duration

Study Progress68%

Mar 2021Oct 2028

First Submitted

Initial submission to the registry

February 13, 2020

Completed

4 days until next milestone

First Posted

Study publicly available on registry

February 17, 2020

Completed

1 year until next milestone

Study Start

First participant enrolled

March 2, 2021

Completed

7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2028

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

May 4, 2026

Status Verified

January 1, 2026

Enrollment Period

7.6 years

First QC Date

February 13, 2020

Last Update Submit

May 1, 2026

Conditions

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

Overall survival (OS)
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 0.042. 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).
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
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.
At 2 years

Secondary Outcomes (7)

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
+2 more secondary outcomes

Other Outcomes (3)

FACT-Leukemia total score
At randomization and at months 3, 6, 9, 12, 15, 18, 24, 30, and 36
The individual components of the FACT-Leukemia
At randomization and at months 3, 6, 9, 12, 15, 18, 24, 30, and 36
Patient-reported health-related quality of life
Up to 36 months

Study Arms (2)

Arm I (delayed V-O)

ACTIVE COMPARATOR

Treatment begins once 2018 IWCLL indications are met. Patients receive obinutuzumab IV over 4 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 22-28 of cycle 1 and on days 1-28 of cycles 2-12. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, collection of blood samples, and bone marrow aspiration and biopsy throughout the trial.

Procedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Computed TomographyBiological: ObinutuzumabOther: Questionnaire AdministrationDrug: Venetoclax

Arm II (early V-O)

EXPERIMENTAL

Treatment begins as soon as eligibility criteria are met. Patients receive obinutuzumab IV over 4 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 22-28 of cycle 1 and on days 1-28 of cycles 2-12. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, collection of blood samples, and bone marrow aspiration and biopsy throughout the trial.