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

A Phase 1/2 Open Label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies

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.

Study Overview

• Status: Active, not recruiting
• 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
• Intervention / Treatment: Drug: Acalabrutinib

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100044
    • Research Site
  • Beijing, China, 100191
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Changzhou, China, 272100
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Fuzhou, China
    • Research Site
  • Haikou, China, 570311
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Harbin, China, 150049
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Hohhot, China, 10050
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210029
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Suzhou, China, 215006
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Tianjin, China, 300020
    • Research Site
  • Urumqi, China, 830054
    • Research Site
  • Xining, China, 810007
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. 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.
2. Chinese subjects at least 18 years of age at the time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
4. Adequate hematological and organ function.
5. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
6. 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.
7. Diagnosis of CLL that meets published diagnostic criteria. Must have received ≥ 1 prior systemic therapies for CLL.
8. Active disease per iwCLL 2018 criteria that requires treatment. (CLL only)
9. Other relapsed/refractory B-cell malignancies without stand of care (phase 1 only).

Exclusion criteria

1. 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.
2. Significant cardiovascular disease.
3. Known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease.
4. Known history of HIV, serologic status reflecting active hepatitis B or C infection.
5. Major surgery within 4 weeks before first dose of study drugs.
6. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
7. Required or received anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon).
8. Prior exposure to a BCR or BCL-2 inhibitor.
9. Use of a strong inhibitor or inducer of CYP3A.
10. Breastfeeding or pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acalabrutinib; Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.	Drug: Acalabrutinib; Acalabrutinib 100 mg orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1: Number of participants with Adverse Events (AEs)	approximately 2 years.
Phase 2: Overall Response Rate (ORR)	up to 3 years
Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) )	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, AUC0-12 (Area under the plasma concentration-time curve (from zero to 12 hours))	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, AUC0-t (Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration))	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after single dose, MR_AUC (metabolite-to-parent ratio, Area under the plasma concentration-time curve (from zero to infinity))	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, AUCτ,ss (Area under the plasma concentration-time curve across the dosing interval at steady state)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, MR_ AUCτ (metabolite-to-parent ratio, Area under the plasma concentration-time curve across the dosing interval)	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, TCP (Temporal change parameter in systemic exposure (also known as: time dependency, temporal parameter change, linearity index); calculated as AUCτ(steady state)/AUC(first dose))	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose))	approximately 1 month.
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax)	approximately 1 month.

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase 1: Tumor response (number of patients with Complete Response (CR), Partial Response (PR), Stable Diseaase (SD), Progression of Disease (PD))	up to 2 years.
Phase 2: Number of participants with Adverse Events (AEs)	approximately 2 year.
Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling)	up to 1 month.
Phase 2: Progression free survival (PFS)	up to 3 years
Phase 2: Duration of Response (DoR)	up to 3 years
Phase 2: Time To Response (TTR)	up to 3 years
Phase 2: Overall Survival (OS)	up to 3 years
Phase 2: Time to Next Treatment (for R/R CLL only)	up to 3 years
Phase 2: Minimum Residual Disease Rate (for R/R CLL only)	up to 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jun Zhu, Prof, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): December 22, 2022
• Study Completion (Anticipated): December 29, 2023

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): April 30, 2019

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Neoplasms; Lymphoma; Leukemia; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: D8220C00007; 2018L02939 (Registry Identifier: CFDA/ NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No