Clinical trial NCT04075292: Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Untreated Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
Acalabrutinib
Progression-free Survival
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-08-30
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Assessed by BICR
timeFrame: 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:
measure: Overall Response Rate (ORR) Assessed by BICR and Investigator
timeFrame: 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)
measure: Duration of Response (DOR) Assessed by BICR and Investigator
timeFrame: 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)
measure: Time to Next Treatment (TTNT)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Minimal Residual Disease (MRD) Negativity Rate
timeFrame: At Cycle 9 (cycle duration: 28 days)
measure: Plasma Concentrations of Acalabrutinib and Its Metabolite ACP-5862
timeFrame: Pre-dose, and at 1, 2, 4 hours post-dose on Day 1 of Cycle 2 (cycle duration: 28 days)
Other outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of study drug (Day 1) up to DCO date of 03 January 2024 (a maximum of approximately 47.5 months)
Locations:
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Baguio City
country: Philippines
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Chiayi
country: Taiwan
facility: Research Site
city: Hualien City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Chinese Academy of Medical Science Affiliated Hospital of Hematology
name: Lugui Qiu, MD
role: PRINCIPAL_INVESTIGATOR
References: