Part1: Advanced B-cell MalignanciesPhase 1NCT03198650
A Phase 1 Study of Acalabrutinib in Japanese Adult Patients With Advanced B-cell Malignancies
A Phase 1 study testing Acalabrutinib and Obinutuzumab in people with Part1: Advanced B-cell Malignancies and Part2: r/rCLL and r/rMCL, run by AstraZeneca at 13 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 120 years
- Conditions the study is for
- Part1: Advanced B-cell Malignancies, Part2: r/rCLL and r/rMCL, Part3: Untreated CLL
- What is being tested?
- Acalabrutinib and Obinutuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 13 sitesJapan
- Study dates
- 27 Jun 2017to 25 Sep 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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>
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- 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:
- 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.
- Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
- Presence of ≥ 5000 μL B lymphocytes in the peripheral blood (at any point since diagnosis)
Who cannot join
- 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)
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- 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.
- History of bleeding diathesis (eg, hemophilia or von Willebrand disease)
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days before first dose of study drug.
- Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole or rabeprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
- Presence of a GI ulcer diagnosed by endoscopy within 3 months before screening.
- Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (ITP).
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Japan13 sites
Research Site
Chiba, 260-8717
Research Site
Chūōku, 104-0045
Research Site
Fukuoka, 812-8582
Research Site
Isehara-shi, 259-1193
Research Site
Izumo-shi, 693-8501
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 460-0001
Research Site
Nagoya, 464-8681
Research Site
Niigata, 951-8520
Research Site
Okayama, 700-8558
Research Site
Sapporo, 060-8638
Research Site
Sendai, 980-8574
Research Site
Suita-shi, 565-0871
About this study
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Acalabrutinib, a Selective and Irreversible Bruton's Tyrosine Kinase Inhibitor, in Japanese Adult Patients With Advanced B-cell Malignancies
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).
- Being tested
- Acalabrutinib, Obinutuzumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Acalabrutinib
ObinutuzumabDrug
Obinutuzumab
| Study group | Role | What they receive |
|---|---|---|
| Part 1 / Part 2 | Experimental | Acalabrutinib Receives: Drug: Acalabrutinib |
| Part 3 | Experimental | Acalabrutinib in combination with Obinutuzumab Receives: Drug: Acalabrutinib; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
Measured: From the date of first dose to Cycle 3 Day 28.
Free Bruton's Tyrosine Kinase (BTK) not occupied by acalabrutinib
Free BTK not occupied by acalabrutinib is measured and BTK occupancy at each timepoint is calculated relative to the predose timepoint. The signal of the predose sample represents 100% free BTK (0% occupied BTK), while each sample incubated with 1 μM exogenous acalabrutinib represents 0% free BTK (100% occupied BTK).
Measured: From the date of first dose to end of treatment visit, up to 80 months
Overall response rate
Defined as the proportion of subjects who achieve a response.
Measured: 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
Defined as the interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause.
Measured: 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
Defined as the interval from the start of acalabrutinib therapy to the earlier of the first documentation of objective disease progression or death from any cause.
Measured: 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
Area under the plasma concentration-time curve (AUC)
PK parameters will be derived using standard non-compartmental methods.
Measured: From the date of first dose to Cycle 3 Day 28
Time to Cmax (tmax)
PK parameters will be derived using standard non-compartmental methods.
Measured: From the date of first dose to Cycle 3 Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2017
- Study start27 Jun 2017
- Primary completion27 Oct 2022
- Study completion25 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Part1: Advanced B-cell MalignanciesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03198650
- Sponsor's protocol ID
- D8220C00001
- Status last verified
- Jun 2026
- First submitted
- 14 Jun 2017
- Last updated
- 29 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Takizawa J, Teshima T, Ennishi D, Ichikawa S, Suzuki R, Kojima A, Takahashi Y, Hayashi N, Kawasumi H, Murayama K, Cheung P, Kawata T, Izutsu K. Safety and efficacy of acalabrutinib and obinutuzumab in treatment-naive chronic lymphocytic leukemia: a Japanese phase 1 study. Leuk Lymphoma. 2024 Nov;65(11):1586-1594. doi: 10.1080/10428194.2024.2370436. Epub 2024 Jul 1.
PubMed 38952054
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Acalabrutinib, a Selective and Irreversible Bruton's Tyrosine Kinase Inhibitor, in Japanese Adult Patients With Advanced B-cell Malignancies
- ClinicalTrials.gov ID
- NCT03198650
- Acronym / sponsor ID
- D8220C00001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2017 (actual)
- Primary completion
- 27 Oct 2022 (actual)
- Study completion
- 25 Sep 2025 (actual)
- First posted
- 26 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 / Part 2 | Experimental | Drug: AcalabrutinibAcalabrutinib |
| Part 3 | Experimental | Drug: Acalabrutinib, Drug: ObinutuzumabAcalabrutinib in combination with Obinutuzumab |
Who may qualify
- Ages
- 20 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAcalabrutinib | Drug | Part 1 / Part 2, Part 3 |
| ObinutuzumabObinutuzumab | Drug | Part 3 |
Primary outcome
Adverse Events (AEs), Serious Adverse Events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability.
Time frame: 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).
Acalabrutinib is considered as safe and tolerable if ≦1 of 6 patients experiences a DLT.
7 secondary outcomes
Maximum plasma concentration (Cmax)
Time frame: From the date of first dose to Cycle 3 Day 28.
Free Bruton's Tyrosine Kinase (BTK) not occupied by acalabrutinib
Time frame: From the date of first dose to end of treatment visit, up to 80 months
Overall response rate
Time frame: 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
Time frame: 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
Time frame: 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
Area under the plasma concentration-time curve (AUC)
Time frame: From the date of first dose to Cycle 3 Day 28
Time to Cmax (tmax)
Time frame: From the date of first dose to Cycle 3 Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Derived from this study: PubMed 38952054Takizawa J, Teshima T, Ennishi D, Ichikawa S, Suzuki R, Kojima A, Takahashi Y, Hayashi N, Kawasumi H, Murayama K, Cheung P, Kawata T, Izutsu K. Safety and efficacy of acalabrutinib and obinutuzumab in treatment-naive chronic lymphocytic leukemia: a Japanese phase 1 study. Leuk Lymphoma. 2024 Nov;65(11):1586-1594. doi: 10.1080/10428194.2024.2370436. Epub 2024 Jul 1.
- Astra Zeneca Clinical Trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Acalabrutinib and Obinutuzumab in people with Part1: Advanced B-cell Malignancies and Part2: r/rCLL and r/rMCL, run by AstraZeneca at 13 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs), Serious Adverse Events (SAEs) and dose-limiting toxicities (DLTs) as a measure of safety and tolerability. (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03198650, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.