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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04075292
Collaborator
(none)
150
Enrollment
51
Locations
2
Arms
57.4
Anticipated Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 20, 2020
Anticipated Primary Completion Date :
Oct 31, 2024
Anticipated Study Completion Date :
Oct 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Acalabrutinib

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity

Drug: Acalabrutinib
acalabrutinib 100 mg twice daily orally
Active Comparator: Rituximab and Chlorambucil

Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles

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)

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

Outcome Measures

Primary Outcome Measures

  1. Progression free survival (PFS) [approximately 50 months]

    Progression free survival is defined as time from randomization until progression or death due to any cause (whichever occurs first)

Secondary Outcome Measures

  1. Objective response rate [approximately 50 months]

  2. Duration of response [approximately 50 months]

  3. Time to next treatment [approximately 50 months]

  4. Overall survival [approximately 50 months]

  5. Minimal residual disease negativity rate [approximately 50 months]

Other Outcome Measures

  1. Incidence of adverse events [approximately 50 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Beijing China 100191
2 Research Site Changchun China 130021
3 Research Site Changsha China 410013
4 Research Site Changzhou China 272100
5 Research Site Fuzhou China 350001
6 Research Site Guangzhou China 510100
7 Research Site Guangzhou China 510515
8 Research Site Guiyang China 550004
9 Research Site Hangzhou China 310003
10 Research Site Hefei China 230001
11 Research Site Hefei China 230031
12 Research Site Lanzhou China 730030
13 Research Site Nanchang China 330006
14 Research Site Nanjing China 210029
15 Research Site Qingdao China 110016
16 Research Site Shanghai China 200025
17 Research Site Shanghai China 200040
18 Research Site Shanghai China 200050
19 Research Site Shenyang China 110001
20 Research Site Shijiazhuang China 050020
21 Research Site Suzhou China 215006
22 Research Site Taiyuan China 030001
23 Research Site Tianjin China 300020
24 Research Site Xuzhou China 221000
25 Research Site Zhengzhou China 450008
26 Research Site Zhengzhou China 450052
27 Research Site Baguio City Philippines 2600
28 Research Site Cebu Philippines 6000
29 Research Site Davao City Philippines 8000
30 Research Site Legazpi City Philippines 4500
31 Research Site Makati Philippines 1229
32 Research Site Manila Philippines 1000
33 Research Site Quezon City Philippines 1112
34 Research Site Chiayi Taiwan 613
35 Research Site Hualien City Taiwan 97002
36 Research Site Kaohsiung Taiwan 833
37 Research Site Taichung Taiwan 404
38 Research Site Taichung Taiwan 40705
39 Research Site Tainan Taiwan 704
40 Research Site Taipei Taiwan 10002
41 Research Site Taipei Taiwan 11217
42 Research Site Taoyuan City Taiwan 333
43 Research Site Bangkok Thailand 10330
44 Research Site Bangkok Thailand 10400
45 Research Site Bangkok Thailand 10700
46 Research Site Chiang Mai Thailand 50200
47 Research Site Hat Yai Thailand 90110
48 Research Site Khon Kaen Thailand 40002
49 Research Site Hanoi Vietnam 100000
50 Research Site Ho Chi Minh city Vietnam
51 Research Site Ho Chi Minh Vietnam 700000

Sponsors and Collaborators

  • AstraZeneca

Investigators

  • Principal Investigator: Lugui Qiu, MD, Chinese Academy of Medical Science Affiliated Hospital of Hematology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT04075292
Other Study ID Numbers:
  • D822BC00001
First Posted:
Aug 30, 2019
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Chronic Lymphocytic Leukemia
Acalabrutinib
Progression-free Survival
Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Rituximab
Acalabrutinib
Chlorambucil

Study Results

No Results Posted as of Aug 4, 2022