Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia

March 3, 2026 updated by: AstraZeneca

A Randomized, Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Acalabrutinib Versus Chlorambucil Plus Rituximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia

This is a randomized, multicenter, open-label, Phase 3 study to evaluate the efficacy and safety of Acalabrutinib versus Chlorambucil plus Rituximab in subjects with Previously Untreated Chronic Lymphocytic Leukemia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patients be randomized in a 1:1 ratio into 2 arms to receive either acalabrutinib monotherapy (Arm A) or rituximab in combination with chlorambucil (Arm B). The primary objective of this study is to compare the efficacy of acalabrutinib relative to chlorambucil plus rituximab in subjects with previously untreated chronic lymphocytic leukemia without del(17p) or TP53 mutation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
155

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100191
        • Research Site
      • Changchun, China, 130021
        • Research Site
      • Changsha, China, 410013
        • Research Site
      • Changzhou, China, 272100
        • Research Site
      • Guangzhou, China, 510100
        • Research Site
      • Guangzhou, China, 510515
        • Research Site
      • Guiyang, China, 550004
        • Research Site
      • Hangzhou, China, 310003
        • Research Site
      • Hefei, China, 230031
        • Research Site
      • Hefei, China, 230001
        • Research Site
      • Nanchang, China, 330006
        • Research Site
      • Nanjing, China, 210029
        • Research Site
      • Qingdao, China, 110016
        • Research Site
      • Shanghai, China, 200025
        • Research Site
      • Shanghai, China, 200040
        • Research Site
      • Shanghai, China, 200050
        • Research Site
      • Shenyang, China, 110001
        • Research Site
      • Shijiazhuang, China, 050020
        • Research Site
      • Suzhou, China, 215006
        • Research Site
      • Taiyuan, China, 030001
        • Research Site
      • Tianjin, China, 300020
        • Research Site
      • Xuzhou, China, 221000
        • Research Site
      • Zhengzhou, China, 450008
        • Research Site
      • Zhengzhou, China, 450052
        • Research Site
  • Philippines
      • Baguio City, Philippines, 2600
        • Research Site
      • Cebu, Philippines, 6000
        • Research Site
      • Davao City, Philippines, 8000
        • Research Site
      • Makati, Philippines, 1229
        • Research Site
      • Manila, Philippines, 1000
        • Research Site
      • Quezon City, Philippines, 1112
        • Research Site
  • Taiwan
      • Chiayi City, Taiwan, 613
        • Research Site
      • Hualien City, Taiwan, 97002
        • Research Site
      • Kaohsiung City, Taiwan, 833
        • Research Site
      • Taichung, Taiwan, 40705
        • Research Site
      • Taichung, Taiwan, 404
        • Research Site
      • Tainan, Taiwan, 704
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Taipei, Taiwan, 11217
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Research Site
      • Bangkok, Thailand, 10400
        • Research Site
      • Bangkok, Thailand, 10700
        • Research Site
      • Chiang Mai, Thailand, 50200
        • Research Site
      • Hat Yai, Thailand, 90110
        • Research Site
      • Khon Kaen, Thailand, 40002
        • Research Site
  • Vietnam
      • Hanoi, Vietnam, 100000
        • Research Site
      • Ho Chi Minh City, Vietnam, 700000
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women: (a) ≥65 years of age OR (b) >18 and <65 years of age, provided that they meet at least one of the following criteria: (i) Creatinine clearance 30 to 69 mL/min using the Cockcroft-Gault equation (iwCLL guidelines) (ii) A score higher than 6 on the Cumulative Illness Rating Score-Geriatric (CIRS G)
  • ECOG performance status of 0, 1, or 2
  • Diagnosis of CLL that meets published diagnostic criteria (Hallek 2018)
  • Active disease per IWCLL 2018 criteria that requires treatment
  • Adequate bone marrow function
  • Adequate renal and hepatic function

Exclusion Criteria:

  • Known detected del(17p) or TP53 mutation
  • Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (eg, Richter's transformation, PLL, or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia
  • History of prior malignancy except for the following: (a) Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study (b) Other cancers not specified above which have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment
  • Significant cardiovascular disease
  • Known history of infection with human immunodeficiency virus (HIV)
  • Serologic status reflecting active hepatitis B or C infection
  • Any active systemic infection (eg, bacterial, viral, or fungal infection) requiring systemic treatment
  • History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
  • Major surgical procedure within 30 days of first dose of study drug
  • Any prior CLL-specific therapies
  • Corticosteroid use >20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
  • For women only: breastfeeding or pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Acalabrutinib
Acalabrutinib will be orally administered until disease progression or unacceptable toxicity
Drug: Acalabrutinib
acalabrutinib 100 mg twice daily orally
Active Comparator: Rituximab and Chlorambucil
Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles
Drug: Rituximab
Rituximab: 375 mg/m2 IV infusion on Day 1 of Cycle 1. 500 mg/m2 IV infusion on Day 1 for each of subsequent cycles (Cycles 2-6)
Drug: Chlorambucil
Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) Assessed by BICR
Time Frame: Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
PFS was defined as the time from randomization to PD (assessed by BICR according to International Workshop on Chronic Lymphocytic Leukaemia [iwCLL] 2018 guideline criteria) or death due to any cause. PD was defined as meeting at least 1 of the below criteria of groups(g) A or B. gA: increase of ≥50% from baseline (BL) or from response in lymph nodes or liver and/or spleen size; any constitutional symptoms; increase of ≥50% over nadir with absolute count ≥ 5×10^9/liter (L) in circulating lymphocyte count (CLC); gB: decrease of ≥50% from BL secondary to CLL in platelet count; decrease of ≥2 gram per deciliter (g/dL) from BL secondary to CLL in hemoglobin (Hb); increase of CLL cells by ≥50% on successive biopsies in bone marrow (BM). Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) Assessed by BICR and Investigator
Time Frame: Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
ORR:percentage of participants with complete response(CR),CR with incomplete BM recovery(CRi), partial response(PR)/nodular PR(nPR) assessed by BICR;investigator per IWCLL 2018 criteria at/before initiation of subsequent anti-cancer therapy.CR:No lymph nodes(target lesions)≥1.5 centimeter(cm), spleen<13cm,normal liver;CLC,no constitutional symptoms,platelets≥100,000/microliter(μL),Hb≥11.0 g/dL,BM:normocellular,no CLL cells&B-lymphoid nodules.PR:atleast 2 gA parameters;1 gB parameter need to improve if previously abnormal.If only 1 parameter of both gA,B was abnormal prior to therapy,only 1 needs to improve.gA:Decrease≥50% from BL in lymph nodes,liver & or spleen size,CLC;any constitutional symptoms, gB:platelet≥100,000/μL or increase 50% over BL;Hb≥11g/dL or increase≥50% over BL;BM:presence of CLL cells/B-lymphoid nodules/not done.CRi:all CR criteria+persistent anemia,thrombocytopenia or neutropenia unrelated to CLL,related to drug toxicity.nPR:CR+presence of B-lymphoid nodules in BM.
Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
Duration of Response (DOR) Assessed by BICR and Investigator
Time Frame: Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
DOR was defined as the time from response (date of first documented response) to PD or death (absence of PD) as judged by BICR and investigator. PD was defined as meeting at least 1 of the below criteria of group A or group B. Group A: Increase of ≥ 50% from BL or from response in lymph nodes or liver and/or spleen size; any constitutional symptoms; increase of ≥50% over nadir with absolute count ≥ 5×10^9/L in CLC; group B: decrease of ≥50% from BL secondary to CLL in platelet count; decrease of ≥2 g/dL from BL secondary to CLL in hemoglobin; increase of CLL cells by ≥50% on successive biopsies in marrow. Median DOR was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD or death, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
Time to Next Treatment (TTNT)
Time Frame: Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD, and survival follow-ups performed every 12 weeks thereafter, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
TTNT was defined as the time from the date of randomization to the date of initiation of non-protocol-specified anti-CLL therapy (either medication or radiotherapy for CLL) or death from any cause, whichever occurred first. Median TTNT was calculated using Kaplan-Meier method and its CI was calculated using Brookmeyer-Crowley method.
Response evaluations performed every 12 weeks from Cycle 4 Day 1 to Cycle 25, then every 24 weeks until PD, and survival follow-ups performed every 12 weeks thereafter, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
Overall Survival (OS)
Time Frame: From date of randomization until death due to any cause, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
OS was defined as the time from the date of randomization until death due to any cause. The median OS was calculated using Kaplan-Meier method and its CI was calculated using Brookmeyer-Crowley method.
From date of randomization until death due to any cause, up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
Minimal Residual Disease (MRD) Negativity Rate
Time Frame: At Cycle 9 (cycle duration: 28 days)
The MRD negative rate was defined as the percentage of participants with MRD-negativity (defined as <1 CLL cell per 10,000 leukocytes) measured in the peripheral blood by flow cytometry.
At Cycle 9 (cycle duration: 28 days)
Plasma Concentrations of Acalabrutinib and Its Metabolite ACP-5862
Time Frame: Pre-dose, and at 1, 2, 4 hours post-dose on Day 1 of Cycle 2 (cycle duration: 28 days)
Blood samples were collected to determine the concentration of acalabrutinib and its metabolite ACP-5862 in plasma.
Pre-dose, and at 1, 2, 4 hours post-dose on Day 1 of Cycle 2 (cycle duration: 28 days)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: From first dose of study drug (Day 1) up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
An adverse event (AE) was any untoward medical occurrence (other than progression of the malignancy under evaluation) in participant or clinical study participant administered medicinal product and which does not necessarily had a causal relationship with treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was life-threatening, required in-participant hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred or worsened in severity on or after date of the first dose of study drug up to 30 days after last dose of study drug or prior to initiation of a new anti-CLL therapy, whichever occurred first.
From first dose of study drug (Day 1) up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lugui Qiu, MD, Chinese Academy of Medical Science Affiliated Hospital of Hematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 3, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 19, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D822BC00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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