Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies

NCT03932331 | Active Not Recruiting Phase 1 Results

• 2 other identifiers: D8220C000072018L02939
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 23

Brief Summary

This is an open-label, two-part study to assess the safety, tolerability, pharmacokinetics and clinical efficacy of acalabrutinib in Chinese adult subjects with R/R MCL, CLL and other B-cell malignancies. The study is divided into 2 parts: Phase 1 portion and Phase 2 portion.

Conditions

Phase I: Relapsed or Refractory B-cell Malignancies; Phase II Cohort A: Relapsed or Refractory Mantle Cell Lymphoma; Phase II Cohort B: Relapsed or Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (19)

• Phase I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A SAE is an AE occurring during any study phase, that fulfils 1 or more of the following criteria: death, life-threatening, in-participant hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, and an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above. AEs leading to discontinuation of acalabrutinib were those with action taken was 'Drug Permanently Discontinued' for acalabrutinib.

  From the first dose administration up to 30 days following the date of last dose of study treatment, approximately 25 months.

• Phase I: Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUCinf) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the AUCinf of acalabrutinib and ACP-5862 in plasma. The AUCinf was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Area Under the Plasma Concentration-Time Curve From Zero to 12 Hours (AUC0-12) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the AUC0-12 of acalabrutinib and ACP-5862 in plasma. The AUC0-12 was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1

• Phase I: Area Under the Plasma Concentration-Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUClast) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the AUClast of acalabrutinib and ACP-5862 in plasma. The AUClast was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Maximum Observed Plasma Drug Concentration (Cmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the Cmax of acalabrutinib and ACP-5862 in plasma. The Cmax was determined using non-compartmental method.

  Single dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1; Multiple dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Time to Reach Maximum Observed Concentration (Tmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the tmax of acalabrutinib and ACP-5862 in plasma. The tmax was determined using non-compartmental method.

  Single dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1; Multiple dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Apparent Total Body Clearance of Drug (CL/F) of Acalabrutinib Post Single and Multiple Dose of Acalabrutinib

  Urine samples were collected to determine the CL/F of acalabrutinib. The CL/F was determined using non-compartmental method.

  Single dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1; Multiple dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Apparent Volume of Distribution (Vz/F) of Acalabrutinib Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the Vz/F of acalabrutinib in plasma. The Vz/F was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Terminal Elimination Rate Constant (λz) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the λz of acalabrutinib and ACP-5862 in plasma. The λz was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Terminal Phase Half-Life (t1/2λz) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the t1/2λz of acalabrutinib and ACP-5862 in plasma. The t1/2λz was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Metabolite/Parent Drug Cmax Ratio (MRCmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the MRCmax of acalabrutinib and ACP-5862 in plasma. The MRCmax was determined using non-compartmental method.

  Single dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1; Multiple dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Metabolite/Parent Drug AUC Ratio (MRAUCinf) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

  Blood samples were collected to determine the MRAUCinf of acalabrutinib in plasma. The MRAUCinf was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

• Phase I: Area Under the Plasma Concentration-Time Curve Across the Dosing Interval (AUCτ) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the AUCτ of acalabrutinib and ACP-5862 in plasma. The AUCτ was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Minimum Observed Plasma Drug Concentration (Cmin) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the Cmin of acalabrutinib and ACP-5862 in plasma. The Cmin was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Metabolite/Parent Drug AUCτ Ratio (MRAUCτ) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the MRAUCτ of acalabrutinib and ACP-5862 in plasma. The MRAUCτ was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Temporal Change Parameter (TCP) in Systemic Exposure of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the TCP of acalabrutinib and ACP-5862 in plasma. The TCP in systemic exposure was calculated as AUCτ (steady state)/AUCinf (first dose). The TCP was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Accumulation Ratio of AUCτ (Rac AUC) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the Rac AUC of acalabrutinib and ACP-5862 in plasma. The Rac AUC was calculated as AUCτ (steady state)/AUCτ (first dose). The Rac AUC was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase I: Accumulation Ratio of Cmax (Rac Cmax) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

  Blood samples were collected to determine the Rac Cmax of acalabrutinib and ACP-5862 in plasma. The Rac Cmax was calculated as Cmax (steady state)/Cmax (first dose). The Rac Cmax was determined using non-compartmental method.

  Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

• Phase II: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR)

  The ORR \[based on International workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria as assessed by the BICR\] was defined as the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR), and partial response (PR). The ORR and the corresponding 95% 2-sided confidence interval (CI) of ORR were presented based on Clopper-Pearson exact method.

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

Secondary Outcomes (10)

• Phase I: Best Overall Response (BOR) Assessed by Investigator in Participants With R/R CLL

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days thereafter or more frequently at the investigator's discretion, approximately 25 months

• Phase I: Best Overall Response Assessed by Investigator in Participants With R/R MCL

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days thereafter or more frequently at the investigator's discretion, approximately 25 months

• Phase II: ORR Assessed by Investigator

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

• Phase II: Duration of Response (DoR) Assessed by BICR and Investigator

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

• Phase II: Progression-Free Survival (PFS) Assessed by BICR and Investigator

  Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

Study Arms (1)

Acalabrutinib

EXPERIMENTAL

Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Acalabrutinib 100 mg orally twice daily

Acalabrutinib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Chinese subjects at least 18 years of age at the time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Adequate hematological and organ function.
• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
• Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5). Disease had relapsed after or been refractory to previous treatment.
• Diagnosis of CLL that meets published diagnostic criteria. Must have received ≥ 1 prior systemic therapies for CLL.
• Active disease per iwCLL 2018 criteria that requires treatment. (CLL only)
• Other relapsed/refractory B-cell malignancies without stand of care (phase 1 only).

You may not qualify if:

• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to \<2 years.
• Significant cardiovascular disease.
• Known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease.
• Known history of HIV, serologic status reflecting active hepatitis B or C infection.
• Major surgery within 4 weeks before first dose of study drugs.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• Required or received anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon).
• Prior exposure to a BCR or BCL-2 inhibitor.
• Use of a strong inhibitor or inducer of CYP3A.
• Breastfeeding or pregnant.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (23)

Research Site

Beijing, 100044, China

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Beijing, 100142, China

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Beijing, 100191, China

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Changchun, 130021, China

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Changsha, 410008, China

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Changzhou, 272100, China

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Chengdu, 610041, China

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Fuzhou, China

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Haikou, 570311, China

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Hangzhou, 310003, China

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Hangzhou, 310022, China

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Harbin, 150049, China

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Hefei, 230031, China

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Hohhot, 10050, China

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Nanchang, 330006, China

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Nanjing, 210029, China

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Shanghai, 200032, China

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Suzhou, 215006, China

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Tianjin, 300020, China

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Tianjin, 300060, China

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Ürümqi, 830054, China

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Xining, 810007, China

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Zhengzhou, 450008, China

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Related Publications (2)

• Yang S, Huang H, Zhou K, Zhao X, Han Y, Li L, Wang Y, Liu X, Li J. Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial. Ann Hematol. 2025 Jan;104(1):701-712. doi: 10.1007/s00277-024-05978-4. Epub 2024 Sep 14.

  PMID: 39271521 DERIVED

• Song Y, Li J, Zhou K, Ke X, Cai Z, Zhang H, Yao T, Xia Z, Wang Y, Lai P, Liu X, Zhu J. Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma. Leuk Lymphoma. 2024 May;65(5):647-652. doi: 10.1080/10428194.2024.2310141. Epub 2024 Apr 1.

  PMID: 38557285 DERIVED

Related Links

• Related Info
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MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Jun Zhu, Prof

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 30, 2019
• Study Start: April 29, 2020
• Primary Completion: December 22, 2022
• Study Completion (Estimated): June 24, 2026
• Last Updated: April 20, 2026
• Results First Posted: March 20, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

CN (23)