Untreated Chronic Lymphocytic LeukemiaPhase 3NCT04075292
Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia
A Phase 3 study testing Acalabrutinib, Rituximab and Chlorambucil in people with Untreated Chronic Lymphocytic Leukemia, run by AstraZeneca at 46 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Untreated Chronic Lymphocytic Leukemia
- What is being tested?
- Acalabrutinib, Rituximab and Chlorambucil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 46 sitesin 5 countries
- Study dates
- 20 Jan 2020to 1 Jan 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
46 sites in 5 countries.
46 sites in 5 countries
China24 sites
Research Site
Beijing, 100191
Research Site
Changchun, 130021
Research Site
Changsha, 410013
Research Site
Changzhou, 272100
Research Site
Guangzhou, 510100
Research Site
Guangzhou, 510515
Research Site
Guiyang, 550004
Research Site
Hangzhou, 310003
Research Site
Hefei, 230001
Research Site
Hefei, 230031
Research Site
Nanchang, 330006
Research Site
Nanjing, 210029
Research Site
Qingdao, 110016
Research Site
Shanghai, 200025
Research Site
Shanghai, 200040
Research Site
Shanghai, 200050
Research Site
Shenyang, 110001
Research Site
Shijiazhuang, 050020
Research Site
Suzhou, 215006
Research Site
Taiyuan, 030001
Research Site
Tianjin, 300020
Research Site
Xuzhou, 221000
Research Site
Zhengzhou, 450008
Research Site
Zhengzhou, 450052
Taiwan8 sites
Research Site
Chiayi City, 613
Research Site
Hualien City, 97002
Research Site
Kaohsiung City, 833
Research Site
Taichung, 404
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 11217
Philippines6 sites
Research Site
Baguio City, 2600
Research Site
Cebu, 6000
Research Site
Davao City, 8000
Research Site
Makati, 1229
Research Site
Manila, 1000
Research Site
Quezon City, 1112
Thailand6 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Bangkok, 10700
Research Site
Chiang Mai, 50200
Research Site
Hat Yai, 90110
Research Site
Khon Kaen, 40002
Vietnam2 sites
Research Site
Hanoi, 100000
Research Site
Ho Chi Minh City, 700000
About this study
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
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.
Read the 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.
- Conditions
- Untreated Chronic Lymphocytic Leukemia
- Being tested
- Acalabrutinib, Rituximab, Chlorambucil
- Keywords
- Chronic Lymphocytic Leukemia, Acalabrutinib, Progression-free Survival
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
acalabrutinib 100 mg twice daily orally
RituximabDrug
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)
ChlorambucilDrug
Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib | Experimental | Acalabrutinib will be orally administered until disease progression or unacceptable toxicity Receives: Drug: Acalabrutinib |
| Rituximab and Chlorambucil | Active comparator | Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles Receives: Drug: Rituximab; Drug: Chlorambucil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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
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.
Measured: At Cycle 9 (cycle duration: 28 days)
Plasma Concentrations of Acalabrutinib and Its Metabolite ACP-5862
Blood samples were collected to determine the concentration of acalabrutinib and its metabolite ACP-5862 in plasma.
Measured: Pre-dose, and at 1, 2, 4 hours post-dose on Day 1 of Cycle 2 (cycle duration: 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start20 Jan 2020
- Primary completion3 Jan 2024
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Untreated Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lugui Qiu, MD, Principal investigator, Chinese Academy of Medical Science Affiliated Hospital of Hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04075292
- Sponsor's protocol ID
- D822BC00001
- Status last verified
- Sep 2026
- First submitted
- 19 Aug 2019
- Last updated
- 14 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.