search
Back to results

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

Primary Purpose

Untreated Chronic Lymphocytic Leukemia

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Acalabrutinib
Rituximab
Chlorambucil
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Untreated Chronic Lymphocytic Leukemia focused on measuring Chronic Lymphocytic Leukemia, Acalabrutinib, Progression-free Survival

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Acalabrutinib

Rituximab and Chlorambucil

Arm Description

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity

Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Objective response rate
Duration of response
Time to next treatment
Overall survival
Minimal residual disease negativity rate

Full Information

First Posted
August 19, 2019
Last Updated
June 22, 2023
Sponsor
AstraZeneca
search

1. Study Identification

Unique Protocol Identification Number
NCT04075292
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 20, 2020 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Untreated Chronic Lymphocytic Leukemia
Keywords
Chronic Lymphocytic Leukemia, Acalabrutinib, Progression-free Survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
155 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acalabrutinib
Arm Type
Experimental
Arm Description
Acalabrutinib will be orally administered until disease progression or unacceptable toxicity
Arm Title
Rituximab and Chlorambucil
Arm Type
Active Comparator
Arm Description
Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Intervention Description
acalabrutinib 100 mg twice daily orally
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Chlorambucil
Intervention Description
Chlorambucil: 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6
Primary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
Progression free survival is defined as time from randomization until progression or death due to any cause (whichever occurs first)
Time Frame
approximately 50 months
Secondary Outcome Measure Information:
Title
Objective response rate
Time Frame
approximately 50 months
Title
Duration of response
Time Frame
approximately 50 months
Title
Time to next treatment
Time Frame
approximately 50 months
Title
Overall survival
Time Frame
approximately 50 months
Title
Minimal residual disease negativity rate
Time Frame
approximately 50 months
Other Pre-specified Outcome Measures:
Title
Incidence of adverse events
Time Frame
approximately 50 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lugui Qiu, MD
Organizational Affiliation
Chinese Academy of Medical Science Affiliated Hospital of Hematology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Research Site
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
Research Site
City
Changsha
ZIP/Postal Code
410013
Country
China
Facility Name
Research Site
City
Changzhou
ZIP/Postal Code
272100
Country
China
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510100
Country
China
Facility Name
Research Site
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
Research Site
City
Guiyang
ZIP/Postal Code
550004
Country
China
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230001
Country
China
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230031
Country
China
Facility Name
Research Site
City
Nanchang
ZIP/Postal Code
330006
Country
China
Facility Name
Research Site
City
Nanjing
ZIP/Postal Code
210029
Country
China
Facility Name
Research Site
City
Qingdao
ZIP/Postal Code
110016
Country
China
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Research Site
City
Shanghai
ZIP/Postal Code
200050
Country
China
Facility Name
Research Site
City
Shenyang
ZIP/Postal Code
110001
Country
China
Facility Name
Research Site
City
Shijiazhuang
ZIP/Postal Code
050020
Country
China
Facility Name
Research Site
City
Suzhou
ZIP/Postal Code
215006
Country
China
Facility Name
Research Site
City
Taiyuan
ZIP/Postal Code
030001
Country
China
Facility Name
Research Site
City
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Research Site
City
Xuzhou
ZIP/Postal Code
221000
Country
China
Facility Name
Research Site
City
Zhengzhou
ZIP/Postal Code
450008
Country
China
Facility Name
Research Site
City
Zhengzhou
ZIP/Postal Code
450052
Country
China
Facility Name
Research Site
City
Baguio City
ZIP/Postal Code
2600
Country
Philippines
Facility Name
Research Site
City
Cebu
ZIP/Postal Code
6000
Country
Philippines
Facility Name
Research Site
City
Davao City
ZIP/Postal Code
8000
Country
Philippines
Facility Name
Research Site
City
Makati
ZIP/Postal Code
1229
Country
Philippines
Facility Name
Research Site
City
Manila
ZIP/Postal Code
1000
Country
Philippines
Facility Name
Research Site
City
Quezon City
ZIP/Postal Code
1112
Country
Philippines
Facility Name
Research Site
City
Chiayi
ZIP/Postal Code
613
Country
Taiwan
Facility Name
Research Site
City
Hualien City
ZIP/Postal Code
97002
Country
Taiwan
Facility Name
Research Site
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Research Site
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Research Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Research Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Research Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Research Site
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Research Site
City
Hat Yai
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Research Site
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Research Site
City
Hanoi
ZIP/Postal Code
100000
Country
Vietnam
Facility Name
Research Site
City
Ho Chi Minh city
Country
Vietnam
Facility Name
Research Site
City
Ho Chi Minh
ZIP/Postal Code
700000
Country
Vietnam

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

We'll reach out to this number within 24 hrs