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

Untreated Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04075292
• Other study ID #: D822BC00001
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 20, 2020
• Est. completion date: November 29, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 155
• Est. completion date: November 29, 2024
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Untreated Chronic Lymphocytic Leukemia

Intervention

Drug:
• Acalabrutinib
acalabrutinib 100 mg twice daily orally
• 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)
• Chlorambucil
Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Suzhou
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Xuzhou
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
Philippines	Research Site	Baguio City
Philippines	Research Site	Cebu
Philippines	Research Site	Davao City
Philippines	Research Site	Makati
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Taiwan	Research Site	Chiayi
Taiwan	Research Site	Hualien City
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

China,  Philippines,  Taiwan,  Thailand,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events		approximately 50 months
Primary	Progression free survival (PFS)	Progression free survival is defined as time from randomization until progression or death due to any cause (whichever occurs first)	approximately 50 months
Secondary	Objective response rate		approximately 50 months
Secondary	Duration of response		approximately 50 months
Secondary	Time to next treatment		approximately 50 months
Secondary	Overall survival		approximately 50 months
Secondary	Minimal residual disease negativity rate		approximately 50 months