Loading clinical trials...

A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE3

A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

A Phase III Prospective, Multicenter, Randomized, Open-Label Trial of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT05057494•AstraZeneca

View on ClinicalTrials.gov

Summary

A study of acalabrutinib plus venetoclax (AV) versus venetoclax plus obinutuzumab (VO) in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description

This is a phase III prospective, multicenter, randomized, open-label trial. After completion of the screening period, eligible participants will be randomized in a 1:1 ratio to each of the following intervention arms: Arm A: Minimal Residual Disease (MRD)-limited finite AV therapy Arm B: MRD-limited finite VO therapy The study consists of screening, treatment, and post-intervention follow-up periods. Participants will undergo safety and efficacy assessments during each period for each study arm. The duration of individual participant involvement in the study will be approximately 5 years. All participants who discontinue study intervention will be followed for safety assessments and survival status. Safety/survival follow-up is not required if the participant permanently discontinues study intervention due to withdrawal of consent, loss to follow-up, or death

Eligibility

Age

18 - 130 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Participant must be ≥ 18 years at the time of signing the consent form.
•2. Documented TN CLL/SLL requiring treatment according to iwCLL guidelines 2018 (Hallek et al 2018).
•3. Adequate BM function independent of growth factor or platelet transfusion support within 2 weeks of screening initiation as follows:
•1. Absolute neutrophil count ≥ 1.0 × 10 9 /L; absolute neutrophil count ≥ 500 cells/μL (≥ 0.50 × 109/L) with documented bone marrow (BM) involvement of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL).
•2. Platelet counts ≥ 30 × 10 9 /L; platelet count ≥ 10 × 10 9 /L in participants with documented BM involvement of CLL/SLL.
•4. Estimated CrCL of ≥ 30 mL/min calculated by Cockcroft-Gault (using actual body weight) or serum creatinine \< 2 × ULN,
•Males:
•CrCL (mL/min) = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL)
•Females:
•CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL)
+6 more criteria

Exclusion Criteria

•1. As judged by the investigator, any evidence of past or current diseases that, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize their safety or compliance with the protocol or would put the study at risk.
•2. Clinically significant cardiovascular disease, such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction, within 6 months of screening or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: Participants with controlled, asymptomatic atrial fibrillation can enroll in the study.
•3. Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
•4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
•5. History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study intervention.
•6. Child-Pugh B/C liver cirrhosis.
•7. History of prior or current malignancy (including but not limited to known central nervous system involvement such as by CLL/SLL, leptomeningeal disease, or spinal cord compression, known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome) that could affect compliance with the protocol or interpretation of results. Possible examples where compliance or data interpretation may not be affected could include the following, per physician discretion.
•1. Curatively treated basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
•2. Other cancers that have been curatively treated from which the participant is disease-free for ≥ 3 years without further treatment.
•8. An individual organ system dysfunction limiting the ability to receive the study intervention or any other life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participants' safety or interfere with the absorption, distribution, metabolism, or excretion of the study interventions (eg, refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, previous significant bowel resection, or impaired resorption in the gastrointestinal tract).
+22 more criteria

Locations (38)

Research Site

Tucson, Arizona, United States

Research Site

La Jolla, California, United States

Research Site

Longmont, Colorado, United States

Research Site

Jacksonville, Florida, United States

Research Site

Boston, Massachusetts, United States

Research Site

St Louis, Missouri, United States

Research Site

Buffalo, New York, United States

Research Site

New Hyde Park, New York, United States

Research Site

New York, New York, United States

Research Site

Rochester, New York, United States

Key Dates

Start Date

September 12, 2022

Primary Completion Date

July 15, 2027

Completion Date

April 10, 2029

Last Updated

February 18, 2026

Enrollment

607

ACTUAL participants

Conditions

Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Interventions

Acalabrutinib

DRUG

Venetoclax

DRUG

Obinutuzumab

DRUG