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

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03932331

Collaborator

(none)

105

Enrollment

Locations

Arm

Anticipated Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Acalabrutinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 29, 2020

Anticipated Primary Completion Date :

Jun 29, 2022

Anticipated Study Completion Date :

Dec 29, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Acalabrutinib

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

Drug: Acalabrutinib

Acalabrutinib 100 mg orally twice daily

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beijing	China	100044
2	Research Site	Beijing	China	100142
3	Research Site	Beijing	China	100191
4	Research Site	Changchun	China	130021
5	Research Site	Changsha	China	410008
6	Research Site	Changzhou	China	272100
7	Research Site	Chengdu	China	610041
8	Research Site	Fuzhou	China
9	Research Site	Haikou	China	570311
10	Research Site	Hangzhou	China	310003
11	Research Site	Hangzhou	China	310022
12	Research Site	Harbin	China	150049
13	Research Site	Hefei	China	230031
14	Research Site	Hohhot	China	10050
15	Research Site	Nanchang	China	330006
16	Research Site	Nanjing	China	210029
17	Research Site	Shanghai	China	200032
18	Research Site	Suzhou	China	215006
19	Research Site	Tianjin	China	300020
20	Research Site	Tianjin	China	300060
21	Research Site	Urumqi	China	830054
22	Research Site	Xining	China	810007
23	Research Site	Zhengzhou	China	450008