A Phase 1 Study of Acalabrutinib in Japanese Adult Patients With Advanced B-cell Malignancies

NCT03198650 | Active Not Recruiting Phase 1

• 1 other identifier: D8220C00001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

Brief Summary

This is a multicenter, open-label Phase 1 study of acalabrutinib, a selective and irreversible Bruton's tyrosine kinase inhibitor, in Japanese adult patients with advanced B-cell malignancies. This study is divided into 3 parts: Part 1 (dose-confirmation phase), Part 2 (dose-expansion phase) and Part 3 (dose-confirmation phase for combination therapy).

Conditions

Part1: Advanced B-cell Malignancies; Part2: r/rCLL and r/rMCL; Part3: Untreated CLL

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs), Serious Adverse Events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability.

  Acalabrutinib is considered as safe and tolerable if ≦1 of 6 patients experiences a DLT.

  From the first dose of study treatment to data cut-off date defined as 2 years after last subject enrolled. In Part 1, DLT will be evaluated in Cycle 1 (28 days). In Part 3, DLT will be evaluated in Cycle 2 (28 days).

Secondary Outcomes (7)

• Maximum plasma concentration (Cmax)

  From the date of first dose to Cycle 3 Day 28.

• Free Bruton's Tyrosine Kinase (BTK) not occupied by acalabrutinib

  From the date of first dose to end of treatment visit, up to 80 months

• Overall response rate

  From the start of acalabrutinib therapy to earlier of the first documentation of objective disease progression or death from any cause, whichever came first up to 80 months

• Duration of Response

  From the start of acalabrutinib therapy to earlier of the first documentation of objective disease progression or death from any cause, whichever came first up to 80 months

• Progression free survival

  From the start of acalabrutinib therapy to earlier of the first documentation of objective disease progression or death from any cause, whichever came first up to 80 months

Study Arms (2)

Part 1 / Part 2

EXPERIMENTAL

Acalabrutinib

Drug: Acalabrutinib

Part 3

EXPERIMENTAL

Acalabrutinib in combination with Obinutuzumab

Drug: Acalabrutinib; Drug: Obinutuzumab

Interventions

Acalabrutinib DRUG

Acalabrutinib

Part 1 / Part 2; Part 3

Obinutuzumab DRUG

Obinutuzumab

Part 3

Eligibility Criteria

• Age: 20 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
• Japanese subjects at least 20 years of age at the time of study entry.
• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of a ≥ 2.0 cm lesion as measured in the longest dimension by computerised tomography \[CT\] scan). Note: Not applicable to subjects with Chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM)
• Eastern Co-operative Oncology Group (ECOG) Performance Status (PS) of ≤ 2
• Adequate organ function defined as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 × institutional upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN except in the case of subjects with documented Gilbert's disease, ≤ 2.5 × ULN
• Serum amylase ≤1.5 × ULN or serum lipase ≤1.5 × ULN \<Part2\>
• Relapsed or refractory CLL/SLL: Confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to ≥ 1 prior therapy for CLL/SLL, and has active disease meeting IWCLL 2008 criteria (Hallek 2008).
• Relapse or refractory MCL: Confirmed diagnosis of MCL, which has relapsed after,or been refractory to ≥ 1 prior therapy for MCL, and documented failure to achieve at least PR with, or documented disease progression after, the most recent treatment regimen.
• \<Part3\>
• Japanese subjects:
• ≥ 65 years of age OR
• ≥ 20 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. ii. A score higher that 6 on the Cumulative Illness Rating Scale-Geriatric
• Diagnosis of CD20+ CLL that meets published diagnostic criteria (Hallek 2008):
• Monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.

You may not qualify if:

• History of other invasive malignancy within 2 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured.
• A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification (New York Heart Association Functional Classification 1994).
• Malabsorption syndrome, disease significantly affecting GI function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery such as gastric bypass.
• Known CNS involvement by lymphoma/leukemia
• Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome (for CLL/SLL)
• Receipt of any biological or immunological based therapies (including experimental therapies) for leukaemia or lymphoma or myeloma (including, but not limited to, MAb therapy such as rituximab, or cancer vaccine therapies) within 4 weeks prior to the first dose of acalabrutinib.
• Any prior therapy with BCR inhibitors (eg, BTK, PI3Kδ, or SYK inhibitors) or BCL-2 inhibitors (eg, venetoclax/ABT-199)
• Known history of HIV, serologic status reflecting active hepatitis B or C infection,or any uncontrolled active systemic infection.
• History of stroke or intracranial haemorrhage within 6 months prior to first dose of study drug.
• Ongoing, drug-induced liver injury, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
• History of or ongoing drug-induced pneumonitis
• Estimated creatinine clearance of \< 30 mL/min, calculated using the formula of Cockcroft and Gault \[(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female\]
• Significant screening electrocardiogram (ECG) abnormalities including left bundle-branch block, 2nd degree AV block type II, 3rd-degree AV block, Grade ≥ 2 bradycardia, and the average QT interval corrected for heart rate (QTc) from the three screening ECGs must be \> 480 msec (calculated using Fridericia's formula: QT/RR0.33)
• Concurrent participation in another therapeutic clinical trial.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (14)

Research Site

Chiba, 260-8717, Japan

Location

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Fukuoka, 812-8582, Japan

Location

Research Site

Isehara-shi, 259-1193, Japan

Location

Research Site

Izumo-shi, 693-8501, Japan

Location

Research Site

Matsuyama, 791-0280, Japan

Location

Research Site

Nagoya, 460-0001, Japan

Location

Research Site

Nagoya, 464-8681, Japan

Location

Research Site

Niigata, 951-8520, Japan

Location

Research Site

Okayama, 700-8558, Japan

Location

Research Site

Sapporo, 060-8638, Japan

Location

Research Site

Sendai, 980-8574, Japan

Location

Research Site

Shimotsuke-shi, 329-0498, Japan

Location

Research Site

Suita-shi, 565-0871, Japan

Location

Related Links

• Astra Zeneca Clinical Trials website

MeSH Terms

Interventions

acalabrutinib; obinutuzumab

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: June 14, 2017
• First Posted: June 26, 2017
• Study Start: June 27, 2017
• Primary Completion: October 27, 2022
• Study Completion: December 31, 2025
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• 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

JP (14)