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

NCT04075292 | Active Not Recruiting Phase 3 Results DMC

• 1 other identifier: D822BC00001
• Study Type: interventional
• Target: 155
• Locations: 5 countries
• Sites: 46

Brief Summary

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.

Conditions

Untreated Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Acalabrutinib; Progression-free Survival

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Assessed by BICR

  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 Outcomes (6)

• Overall Response Rate (ORR) Assessed by BICR and Investigator

  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

  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)

  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)

  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

  At Cycle 9 (cycle duration: 28 days)

Other Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From first dose of study drug (Day 1) up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)

Study Arms (2)

Acalabrutinib

EXPERIMENTAL

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity

Drug: Acalabrutinib

Rituximab and Chlorambucil

ACTIVE COMPARATOR

Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles

Drug: Rituximab; Drug: Chlorambucil

Interventions

Acalabrutinib DRUG

acalabrutinib 100 mg twice daily orally

Acalabrutinib

Rituximab 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)

Rituximab and Chlorambucil

Chlorambucil DRUG

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

Rituximab and Chlorambucil

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (46)

Research Site

Beijing, 100191, China

Location

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Changchun, 130021, China

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Changsha, 410013, China

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Changzhou, 272100, China

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Guangzhou, 510100, China

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Guangzhou, 510515, China

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Guiyang, 550004, China

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Hangzhou, 310003, China

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Hefei, 230001, China

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Hefei, 230031, China

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Nanchang, 330006, China

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Nanjing, 210029, China

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Qingdao, 110016, China

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Shanghai, 200025, China

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Shanghai, 200040, China

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Shanghai, 200050, China

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Shenyang, 110001, China

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Shijiazhuang, 050020, China

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Suzhou, 215006, China

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Taiyuan, 030001, China

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Tianjin, 300020, China

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Xuzhou, 221000, China

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Zhengzhou, 450008, China

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Zhengzhou, 450052, China

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Baguio City, 2600, Philippines

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Cebu, 6000, Philippines

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Davao City, 8000, Philippines

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Makati, 1229, Philippines

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Manila, 1000, Philippines

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Quezon City, 1112, Philippines

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Chiayi City, 613, Taiwan

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Hualien City, 97002, Taiwan

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Kaohsiung City, 833, Taiwan

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Taichung, 404, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 11217, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Hat Yai, 90110, Thailand

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Khon Kaen, 40002, Thailand

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

Location

Related Links

• CSR synopsis
• Related Info
• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; Rituximab; Chlorambucil

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Lugui Qiu, MD

  Chinese Academy of Medical Science Affiliated Hospital of Hematology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 30, 2019
• Study Start: January 20, 2020
• Primary Completion: January 3, 2024
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 5, 2026
• Results First Posted: January 30, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

TW (8); CN (24); PH (6); VN (2); TH (6)