Back to resultsStudy of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies
Primary Purpose
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
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Acalabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Phase I: Relapsed or Refractory B-cell Malignancies
Eligibility Criteria
Inclusion Criteria
- 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).
Exclusion criteria
- 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.
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Acalabrutinib
Arm Description
Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Phase 1: Number of participants with Adverse Events (AEs)
Phase 2: Overall Response Rate (ORR)
Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) )
Phase 1: Pharmacokinetics Characterization after single dose, AUC0-12 (Area under the plasma concentration-time curve (from zero to 12 hours))
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))
Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration)
Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration)
Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance)
Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution)
Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant)
Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life)
Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration)
Phase 1: Pharmacokinetics Characterization after single dose, MR_AUC (metabolite-to-parent ratio, Area under the plasma concentration-time curve (from zero to infinity))
Phase 1: Pharmacokinetics Characterization after multiple doses, AUCτ,ss (Area under the plasma concentration-time curve across the dosing interval at steady state)
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state)
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state)
Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage)
Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage)
Phase 1: Pharmacokinetics Characterization after multiple doses, MR_ AUCτ (metabolite-to-parent ratio, Area under the plasma concentration-time curve across the dosing interval)
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))
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose))
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax)
Secondary Outcome Measures
Phase 1: Tumor response (number of patients with Complete Response (CR), Partial Response (PR), Stable Diseaase (SD), Progression of Disease (PD))
Phase 2: Number of participants with Adverse Events (AEs)
Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling)
Phase 2: Progression free survival (PFS)
Phase 2: Duration of Response (DoR)
Phase 2: Time To Response (TTR)
Phase 2: Overall Survival (OS)
Phase 2: Time to Next Treatment (for R/R CLL only)
Phase 2: Minimum Residual Disease Rate (for R/R CLL only)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03932331
Brief Title
Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 29, 2020 (Actual)
Primary Completion Date
December 22, 2022 (Actual)
Study Completion Date
December 29, 2023 (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
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
105 (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.
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Intervention Description
Acalabrutinib 100 mg orally twice daily
Primary Outcome Measure Information:
Title
Phase 1: Number of participants with Adverse Events (AEs)
Time Frame
approximately 2 years.
Title
Phase 2: Overall Response Rate (ORR)
Time Frame
up to 3 years
Title
Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) )
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, AUC0-12 (Area under the plasma concentration-time curve (from zero to 12 hours))
Time Frame
approximately 1 month.
Title
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))
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after single dose, MR_AUC (metabolite-to-parent ratio, Area under the plasma concentration-time curve (from zero to infinity))
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, AUCτ,ss (Area under the plasma concentration-time curve across the dosing interval at steady state)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage)
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, MR_ AUCτ (metabolite-to-parent ratio, Area under the plasma concentration-time curve across the dosing interval)
Time Frame
approximately 1 month.
Title
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))
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose))
Time Frame
approximately 1 month.
Title
Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax)
Time Frame
approximately 1 month.
Secondary Outcome Measure Information:
Title
Phase 1: Tumor response (number of patients with Complete Response (CR), Partial Response (PR), Stable Diseaase (SD), Progression of Disease (PD))
Time Frame
up to 2 years.
Title
Phase 2: Number of participants with Adverse Events (AEs)
Time Frame
approximately 2 year.
Title
Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling)
Time Frame
up to 1 month.
Title
Phase 2: Progression free survival (PFS)
Time Frame
up to 3 years
Title
Phase 2: Duration of Response (DoR)
Time Frame
up to 3 years
Title
Phase 2: Time To Response (TTR)
Time Frame
up to 3 years
Title
Phase 2: Overall Survival (OS)
Time Frame
up to 3 years
Title
Phase 2: Time to Next Treatment (for R/R CLL only)
Time Frame
up to 3 years
Title
Phase 2: Minimum Residual Disease Rate (for R/R CLL only)
Time Frame
up to 3 years
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
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).
Exclusion criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhu, Prof
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100142
Country
China
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
410008
Country
China
Facility Name
Research Site
City
Changzhou
ZIP/Postal Code
272100
Country
China
Facility Name
Research Site
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Research Site
City
Fuzhou
Country
China
Facility Name
Research Site
City
Haikou
ZIP/Postal Code
570311
Country
China
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Facility Name
Research Site
City
Hangzhou
ZIP/Postal Code
310022
Country
China
Facility Name
Research Site
City
Harbin
ZIP/Postal Code
150049
Country
China
Facility Name
Research Site
City
Hefei
ZIP/Postal Code
230031
Country
China
Facility Name
Research Site
City
Hohhot
ZIP/Postal Code
10050
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
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Research Site
City
Suzhou
ZIP/Postal Code
215006
Country
China
Facility Name
Research Site
City
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Research Site
City
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
Research Site
City
Urumqi
ZIP/Postal Code
830054
Country
China
Facility Name
Research Site
City
Xining
ZIP/Postal Code
810007
Country
China
Facility Name
Research Site
City
Zhengzhou
ZIP/Postal Code
450008
Country
China
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 in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies
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