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

• ClinicalTrials.gov Identifier: NCT04075292
• Recruitment Status: Recruiting
• First Posted: August 30, 2019
• Last Update Posted: January 18, 2022
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: August 19, 2019
• First Posted Date: August 30, 2019
• Last Update Posted Date: January 18, 2022
• Actual Study Start Date: January 20, 2020
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 29, 2019)

Progression free survival (PFS) [ Time Frame: approximately 50 months ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 29, 2019)

• Objective response rate [ Time Frame: approximately 50 months ]
• Duration of response [ Time Frame: approximately 50 months ]
• Time to next treatment [ Time Frame: approximately 50 months ]
• Overall survival [ Time Frame: approximately 50 months ]
• Minimal residual disease negativity rate [ Time Frame: approximately 50 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures (submitted: August 29, 2019): Incidence of adverse events [ Time Frame: approximately 50 months ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Untreated Chronic Lymphocytic Leukemia

Intervention

• Drug: Acalabrutinib
  acalabrutinib 100 mg twice daily orally
• 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

Study Arms

• Experimental: Acalabrutinib
  Acalabrutinib will be orally administered until disease progression or unacceptable toxicity
  Intervention: Drug: Acalabrutinib
• Active Comparator: Rituximab and Chlorambucil
  Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles
  Interventions:

  • Drug: Rituximab
  • Drug: Chlorambucil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 29, 2019): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2024
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: China, Philippines, Taiwan, Thailand, Vietnam

Administrative Information

• NCT Number: NCT04075292
• Other Study ID Numbers: D822BC00001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• 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.
• 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

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

• PRS Account: AstraZeneca
• Verification Date: January 2022