Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03198650
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE June 14, 2017
First Posted Date  ICMJE June 26, 2017
Last Update Posted Date September 4, 2019
Actual Study Start Date  ICMJE June 27, 2017
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2017)
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 last visit. DLT will be evaluated in Cycle 1 (28 days). ]
Acalabrutinib is considered as safe and tolerable if ≦1 of 6 patients experiences a DLT.
Change History Complete list of historical versions of study NCT03198650 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Maximum plasma concentration (Cmax) [ Time Frame: From the date of first dose to Cycle 3 Day 28. ]
    Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
  • 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 ]
    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).
  • 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 ]
    Defined as the proportion of subjects who achieve a response.
  • 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 ]
    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.
  • 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 ]
    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.
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: From the date of first dose to Cycle 3 Day 28 ]
    PK parameters will be derived using standard non-compartmental methods.
  • Time to Cmax (tmax) [ Time Frame: From the date of first dose to Cycle 3 Day 28 ]
    PK parameters will be derived using standard non-compartmental methods.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2017)
  • Maximum plasma concentration (Cmax) [ Time Frame: From the date of first dose to Cycle 1 Day 28. ]
    Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
  • 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 48 months ]
    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).
  • 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 48 months ]
    Defined as the proportion of subjects who achieve a response.
  • 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 48 months ]
    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.
  • 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 48 months ]
    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.
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: From the date of first dose to Cycle1 Day 28 ]
    PK parameters will be derived using standard non-compartmental methods.
  • Time to Cmax (tmax) [ Time Frame: From the date of first dose to Cycle 1 Day 28 ]
    PK parameters will be derived using standard non-compartmental methods.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Acalabrutinib in Japanese Adult Patients With Advanced B-cell Malignancies
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Part1: Advanced B-cell Malignancies
  • Part2: r/rCLL and r/rMCL
  • Part3: Untreated CLL
Intervention  ICMJE
  • Drug: Acalabrutinib
    Acalabrutinib
  • Drug: Obinutuzumab
    Obinutuzumab
Study Arms  ICMJE
  • Experimental: Part 1 / Part 2
    Acalabrutinib
    Intervention: Drug: Acalabrutinib
  • Experimental: Part 3
    Acalabrutinib in combination with Obinutuzumab
    Interventions:
    • Drug: Acalabrutinib
    • Drug: Obinutuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2019)
34
Original Estimated Enrollment  ICMJE
 (submitted: June 23, 2017)
28
Estimated Study Completion Date  ICMJE July 31, 2023
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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:

    1. ≥ 65 years of age OR
    2. ≥ 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):

    1. 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.
    2. Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
    3. Presence of ≥ 5000 μL B lymphocytes in the peripheral blood (at any point since diagnosis)

Key Exclusion Criteria:

  • 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.
  • 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03198650
Other Study ID Numbers  ICMJE D8220C00001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP