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

NCT ID: NCT04075292

Last Updated: 2025-11-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-20

Study Completion Date

2027-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Untreated Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Acalabrutinib

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity

Group Type EXPERIMENTAL

Acalabrutinib

Intervention Type DRUG

acalabrutinib 100 mg twice daily orally

Rituximab and Chlorambucil

Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

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)

Chlorambucil

Intervention Type DRUG

Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6

Interventions

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Acalabrutinib

acalabrutinib 100 mg twice daily orally

Intervention Type 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)

Intervention Type DRUG

Chlorambucil

Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lugui Qiu, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Science Affiliated Hospital of Hematology

Locations

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Research Site

Beijing, , China

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Changchun, , China

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Changsha, , China

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Changzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guiyang, , China

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Hangzhou, , China

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Hefei, , China

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Hefei, , China

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Nanchang, , China

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Nanjing, , China

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Qingdao, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Shijiazhuang, , China

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Suzhou, , China

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Taiyuan, , China

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Tianjin, , China

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Xuzhou, , China

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Zhengzhou, , China

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Zhengzhou, , China

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Baguio City, , Philippines

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Cebu, , Philippines

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Davao City, , Philippines

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Makati, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Chiayi City, , Taiwan

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Hualien City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Hat Yai, , Thailand

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Khon Kaen, , Thailand

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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China Philippines Taiwan Thailand Vietnam

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D822BC00001

Identifier Type: -

Identifier Source: org_study_id

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