Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02112526
Collaborator
(none)
21
Enrollment
7
Locations
1
Arm
136.8
Anticipated Duration (Months)
3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To characterize the safety profile of acalabrutinib in subjects with relapsed or refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Phase 1b Study of ACP 196 in Subjects With Relapsed or Refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma
Actual Study Start Date :
Aug 7, 2014
Actual Primary Completion Date :
Jun 30, 2020
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Acalabrutinib

Drug: Acalabrutinib
Other Names:
  • ACP-196
  • Outcome Measures

    Primary Outcome Measures

    1. Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. [SAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose.]

      Safety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction.

    Secondary Outcome Measures

    1. Area Under the Plasma Concentration (AUC) [1 Cycle (28 days)]

      To Characterize the Pharmacokinetic parameter AUC of acalabrutinib

    2. Maximum Observed Plasma Concentration (Cmax) [1 Cycle (28 days)]

      To Characterize the Pharmacokinetic parameter Cmax of acalabrutinib

    3. Evaluate Pharmacodynamic (PD) Effects (Done at US Sites Only) [2 Cycles (1 cycle = 28 days) and at end of treatment]

      To evaluate the concentration pharmacodynamic effects of acalabrutinib

    4. Evaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR) [From enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days)]

      To evaluate the activity of acalabrutinib as measured by ORR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Men and women ≥ 18 years of age.

    • Pathologically confirmed de novo ABC DLBCL

    • Relapsed or refractory disease

    • Subjects must have ≥ 1 measurable disease sites

    Exclusion Criteria:
    • 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, or LVEF < 50%

    • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

    • Breast feeding or pregnant

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Research SiteLos AngelesCaliforniaUnited States90095
    2Research SiteAtlantaGeorgiaUnited States30322
    3Research SiteNew YorkNew YorkUnited States10021
    4Research SiteColumbusOhioUnited States43210
    5Research SiteHoustonTexasUnited States77030
    6Research SiteLeicesterUnited KingdomLE1 7RH
    7Research SitePlymouthUnited KingdomPL6 8DH

    Sponsors and Collaborators

    • Acerta Pharma BV

    Investigators

    • Study Director: AstraZeneca Clinical Trials, 1-877-240-9479; information.center@astrazeneca.com

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02112526
    Other Study ID Numbers:
    • ACE-LY-002
    First Posted:
    Apr 14, 2014
    Last Update Posted:
    Mar 23, 2022
    Last Verified:
    Mar 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleCohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Arm/Group DescriptionAcalabrutinib 100mg administered orally (PO) twice daily (BID)Acalabrutinib 100mg administered orally (PO) twice daily (BID)
    Period Title: Overall Study
    STARTED1110
    Enrolled1110
    Received Study Medication1110
    Discontinued Study119
    Subjects Continuing Study Medication01
    COMPLETED01
    NOT COMPLETED119

    Baseline Characteristics

    Arm/Group TitleCohort 1 - Relapse SubjectsCohort 2 - Refractory SubjectsTotal
    Arm/Group DescriptionAcalabrutinib 100mg administered orally (PO) twice daily (BID)Acalabrutinib 100mg administered orally (PO) twice daily (BID)Total of all reporting groups
    Overall Participants111021
    Age (Year) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Year]
    70.7
    (9.57)
    56.9
    (16.26)
    64.1
    (14.66)
    Sex: Female, Male (Count of Participants)
    Female
    6
    54.5%
    5
    50%
    11
    52.4%
    Male
    5
    45.5%
    5
    50%
    10
    47.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    9.1%
    1
    10%
    2
    9.5%
    Not Hispanic or Latino
    10
    90.9%
    9
    90%
    19
    90.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    9.1%
    1
    10%
    2
    9.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    10%
    1
    4.8%
    White
    10
    90.9%
    5
    50%
    15
    71.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    3
    30%
    3
    14.3%
    Region of Enrollment (Count of Participants)
    United States
    9
    81.8%
    6
    60%
    15
    71.4%
    United Kingdom
    2
    18.2%
    4
    40%
    6
    28.6%

    Outcome Measures

    1. Primary Outcome
    TitleSafety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL.
    DescriptionSafety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction.
    Time FrameSAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleCohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Arm/Group DescriptionAcalabrutinib 100mg administered orally (PO) twice daily (BID)Acalabrutinib 100mg administered orally (PO) twice daily (BID)
    Measure Participants1110
    Count of Participants [Participants]
    3
    27.3%
    2
    20%
    2. Secondary Outcome
    TitleArea Under the Plasma Concentration (AUC)
    DescriptionTo Characterize the Pharmacokinetic parameter AUC of acalabrutinib
    Time Frame1 Cycle (28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleMaximum Observed Plasma Concentration (Cmax)
    DescriptionTo Characterize the Pharmacokinetic parameter Cmax of acalabrutinib
    Time Frame1 Cycle (28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleEvaluate Pharmacodynamic (PD) Effects (Done at US Sites Only)
    DescriptionTo evaluate the concentration pharmacodynamic effects of acalabrutinib
    Time Frame2 Cycles (1 cycle = 28 days) and at end of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleEvaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR)
    DescriptionTo evaluate the activity of acalabrutinib as measured by ORR
    Time FrameFrom enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameReported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 697
    Adverse Event Reporting Description
    Arm/Group TitleCohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Arm/Group DescriptionAcalabrutinib 100mg administered orally (PO) twice dailyAcalabrutinib 100mg administered orally (PO) twice daily
    All Cause Mortality
    Cohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/11 (27.3%) 5/10 (50%)
    Serious Adverse Events
    Cohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/11 (36.4%) 5/10 (50%)
    Gastrointestinal disorders
    Abdominal pain0/11 (0%) 2/10 (20%)
    General disorders
    Pyrexia1/11 (9.1%) 1/10 (10%)
    Disease progression1/11 (9.1%) 0/10 (0%)
    Fatigue0/11 (0%) 1/10 (10%)
    Infections and infestations
    Pneumonia0/11 (0%) 1/10 (10%)
    Septic shock1/11 (9.1%) 0/10 (0%)
    Viral infection0/11 (0%) 1/10 (10%)
    Investigations
    Influenza B virus test positive1/11 (9.1%) 0/10 (0%)
    Metabolism and nutrition disorders
    Decreased appetite0/11 (0%) 1/10 (10%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to meninges1/11 (9.1%) 0/10 (0%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure1/11 (9.1%) 1/10 (10%)
    Skin and subcutaneous tissue disorders
    Skin necrosis0/11 (0%) 1/10 (10%)
    Other (Not Including Serious) Adverse Events
    Cohort 1 - Relapse SubjectsCohort 2 - Refractory Subjects
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total10/11 (90.9%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia2/11 (18.2%) 4/10 (40%)
    Increased tendency to bruise1/11 (9.1%) 0/10 (0%)
    Cardiac disorders
    Mitral valve incompetence1/11 (9.1%) 0/10 (0%)
    Ear and labyrinth disorders
    Vertigo1/11 (9.1%) 0/10 (0%)
    Endocrine disorders
    Adrenal insufficiency1/11 (9.1%) 0/10 (0%)
    Eye disorders
    Conjunctival hyperaemia1/11 (9.1%) 0/10 (0%)
    Dry eye1/11 (9.1%) 0/10 (0%)
    Ocular hyperaemia1/11 (9.1%) 0/10 (0%)
    Gastrointestinal disorders
    Diarrhoea8/11 (72.7%) 1/10 (10%)
    Nausea2/11 (18.2%) 3/10 (30%)
    Constipation4/11 (36.4%) 0/10 (0%)
    Vomiting0/11 (0%) 2/10 (20%)
    Abdominal distension1/11 (9.1%) 0/10 (0%)
    Abdominal pain0/11 (0%) 1/10 (10%)
    Abdominal pain upper1/11 (9.1%) 0/10 (0%)
    Ascites0/11 (0%) 1/10 (10%)
    Dysphagia0/11 (0%) 1/10 (10%)
    Faeces discoloured1/11 (9.1%) 0/10 (0%)
    Flatulence1/11 (9.1%) 0/10 (0%)
    Gastrooesophageal reflux disease1/11 (9.1%) 0/10 (0%)
    Stomatitis1/11 (9.1%) 0/10 (0%)
    General disorders
    Fatigue4/11 (36.4%) 4/10 (40%)
    Oedema peripheral2/11 (18.2%) 2/10 (20%)
    Gait disturbance2/11 (18.2%) 0/10 (0%)
    Pyrexia2/11 (18.2%) 0/10 (0%)
    Axillary pain0/11 (0%) 1/10 (10%)
    Chest discomfort0/11 (0%) 1/10 (10%)
    Chills0/11 (0%) 1/10 (10%)
    Injection site bruising1/11 (9.1%) 0/10 (0%)
    Injection site rash0/11 (0%) 1/10 (10%)
    Mucosal inflammation1/11 (9.1%) 0/10 (0%)
    Oedema1/11 (9.1%) 0/10 (0%)
    Peripheral swelling0/11 (0%) 1/10 (10%)
    Hepatobiliary disorders
    Cholecystitis1/11 (9.1%) 0/10 (0%)
    Immune system disorders
    Contrast media allergy1/11 (9.1%) 0/10 (0%)
    Infections and infestations
    Nasopharyngitis1/11 (9.1%) 1/10 (10%)
    Oral candidiasis1/11 (9.1%) 1/10 (10%)
    Sinusitis1/11 (9.1%) 1/10 (10%)
    Cellulitis0/11 (0%) 1/10 (10%)
    Lower respiratory tract infection fungal1/11 (9.1%) 0/10 (0%)
    Oral herpes1/11 (9.1%) 0/10 (0%)
    Rhinitis0/11 (0%) 1/10 (10%)
    Rhinovirus infection1/11 (9.1%) 0/10 (0%)
    Staphylococcal infection1/11 (9.1%) 0/10 (0%)
    Urinary tract infection1/11 (9.1%) 0/10 (0%)
    Urinary tract infection staphylococcal1/11 (9.1%) 0/10 (0%)
    Injury, poisoning and procedural complications
    Contusion2/11 (18.2%) 0/10 (0%)
    Ear abrasion0/11 (0%) 1/10 (10%)
    Fall0/11 (0%) 1/10 (10%)
    Procedural pain0/11 (0%) 1/10 (10%)
    Skin abrasion0/11 (0%) 1/10 (10%)
    Investigations
    Breath sounds abnormal1/11 (9.1%) 0/10 (0%)
    C-reactive protein increased0/11 (0%) 1/10 (10%)
    Cardiac murmur0/11 (0%) 1/10 (10%)
    Weight decreased0/11 (0%) 1/10 (10%)
    Metabolism and nutrition disorders
    Decreased appetite1/11 (9.1%) 2/10 (20%)
    Dehydration1/11 (9.1%) 2/10 (20%)
    Hypokalaemia2/11 (18.2%) 1/10 (10%)
    Hypomagnesaemia1/11 (9.1%) 1/10 (10%)
    Hypocalcaemia1/11 (9.1%) 0/10 (0%)
    Hyponatraemia0/11 (0%) 1/10 (10%)
    Musculoskeletal and connective tissue disorders
    Arthralgia1/11 (9.1%) 2/10 (20%)
    Back Pain2/11 (18.2%) 0/10 (0%)
    Musculoskeletal pain0/11 (0%) 2/10 (20%)
    Neck pain1/11 (9.1%) 1/10 (10%)
    Pain in extremity0/11 (0%) 2/10 (20%)
    Muscular weakness0/11 (0%) 1/10 (10%)
    Musculoskeletal chest pain0/11 (0%) 1/10 (10%)
    Myalgia1/11 (9.1%) 0/10 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain0/11 (0%) 1/10 (10%)
    Nervous system disorders
    Dizziness5/11 (45.5%) 1/10 (10%)
    Headache3/11 (27.3%) 2/10 (20%)
    Carpal tunnel syndrome1/11 (9.1%) 0/10 (0%)
    Memory impairment1/11 (9.1%) 0/10 (0%)
    Neuropathy peripheral1/11 (9.1%) 0/10 (0%)
    Paraesthesia0/11 (0%) 1/10 (10%)
    Peripheral sensory neuropathy0/11 (0%) 1/10 (10%)
    Syncope1/11 (9.1%) 0/10 (0%)
    Psychiatric disorders
    Insomnia2/11 (18.2%) 0/10 (0%)
    Depression0/11 (0%) 1/10 (10%)
    Mental status changes1/11 (9.1%) 0/10 (0%)
    Renal and urinary disorders
    Urinary retention disorders1/11 (9.1%) 0/10 (0%)
    Reproductive system and breast disorders
    Breast swelling0/11 (0%) 1/10 (10%)
    Respiratory, thoracic and mediastinal disorders
    Cough3/11 (27.3%) 3/10 (30%)
    Dyspnoea2/11 (18.2%) 2/10 (20%)
    Pleural effusion1/11 (9.1%) 1/10 (10%)
    Rales1/11 (9.1%) 1/10 (10%)
    Dysphonia0/11 (0%) 1/10 (10%)
    Nasal congestion0/11 (0%) 1/10 (10%)
    Productive cough0/11 (0%) 1/10 (10%)
    throat irritation0/11 (0%) 1/10 (10%)
    Wheezing1/11 (9.1%) 0/10 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia0/11 (0%) 2/10 (20%)
    Ecchymosis1/11 (9.1%) 1/10 (10%)
    Petechiae1/11 (9.1%) 1/10 (10%)
    Rash2/11 (18.2%) 0/10 (0%)
    Actinic Keratosis1/11 (9.1%) 0/10 (0%)
    Erythema0/11 (0%) 1/10 (10%)
    Night sweats1/11 (9.1%) 0/10 (0%)
    Pruritus0/11 (0%) 1/10 (10%)
    Rash maculo-papular1/11 (9.1%) 0/10 (0%)
    Rosacea1/11 (9.1%) 0/10 (0%)
    Skin necrosis0/11 (0%) 1/10 (10%)
    Vascular disorders
    Orthostatic hypotension1/11 (9.1%) 0/10 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationAcerta Pharma LLC
    Phone1-888-292-9613
    Emailacertamc@dlss.com
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02112526
    Other Study ID Numbers:
    • ACE-LY-002
    First Posted:
    Apr 14, 2014
    Last Update Posted:
    Mar 23, 2022
    Last Verified:
    Mar 1, 2022