Clinical Trials /

ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia

NCT02029443

Description:

This study is evaluating the safety and efficacy of a new Bruton tyrosine kinase (Btk) inhibitor, acalabrutinib, for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

ACP-196, a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of <span class="go-doc-concept go-doc-disease">Chronic Lymphocytic Leukemia</span>

Title

  • Brief Title: ACP-196, a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia
  • Official Title: A Phase 1/2, Multicenter, Open-label, and Dose-escalation Study of ACP-196 in Subjects With Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia
  • Clinical Trial IDs

    NCT ID: NCT02029443

    ORG ID: ACE-CL-001

    Trial Conditions

    Chronic Lymphocytic Leukemia

    Small Lymphocytic Lymphoma

    Richter's Syndrome

    Prolymphocytic Leukemia

    Trial Interventions

    Drug Synonyms Arms
    ACP-196 ACP-196

    Trial Purpose

    This study is evaluating the safety and efficacy of a new Bruton tyrosine kinase (Btk)
    inhibitor, ACP-196, for the treatment of chronic lymphocytic leukemia (CLL)/small
    lymphocytic lymphoma (SLL)

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    ACP-196 Experimental ACP-196

    Eligibility Criteria

    Inclusion Criteria:

    - Men and women 18 years of age with a confirmed diagnosis of CLL/SLL, which has
    relapsed after, or been refractory to, 2 previous treatments for CLL/SLL; however,
    subjects with 17p deletion are eligible if they have relapsed after, or been
    refractory to, 1 prior treatment for CLL/SLL.

    - Treatment Naive only: and a) do not want to receive chemoimmunotherapy or b) have
    comorbidities that would preclude chemoimmunotherapy.

    - Richter's Syndrome and Prolymphocytic Leukemia Transformation only: biopsy proven
    DLBCL Richter's transformation or prolymphocytic leukemia transformation.

    - Subjects have been diagnosed with measurable CLL/SLL.

    - Subjects have active disease meeting the IWCLL 2008 published criteria.

    - ECOG performance status of 2.

    - Agreement to use contraception during the study and for 30 days after the last dose
    of study drug if sexually active and able to bear children.

    - Willing and able to participate in all required evaluations and procedures in this
    study protocol including swallowing capsules without difficulty.

    - Ability to understand the purpose and risks of the study and provide signed and dated
    informed consent and authorization to use protected health information (in accordance
    with national and local subject privacy regulations).

    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 has been
    disease free for 2 years or which will not limit survival to < 2 years. Note: these
    cases must be discussed with the Medical Monitor.

    - 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 ACP-196, 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 left ventricular ejection fraction (LVEF) 40%.

    - 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.

    - Any immunotherapy within 4 weeks of first dose of study drug.

    - For subjects with recent chemotherapy or experimental therapy the first dose of study
    drug must occur after 5 times the half-life of the agent(s).

    - Relapsed after, or refractory to, prior BTK inhibitor therapy.

    - Concomitant use of medicines known to cause QT prolongation or Torsades de pointes
    (see Appendix 1).

    - Central nervous system (CNS) involvement by lymphoma

    - Grade 2 toxicity (other than alopecia) continuing from prior anticancer therapy
    including radiation.

    - Known history of human immunodeficiency virus (HIV) or active infection with
    hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active
    systemic infection.

    - Major surgery within 4 weeks before first dose of study drug.

    - ANC < 0.75 x 109/L or platelet count < 50 x 109/L unless there is bone marrow
    involvement.

    - Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x
    ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or
    alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.

    - Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN.

    - Significant screening ECG abnormalities including left bundle branch block, 2nd
    degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and QTc
    480 ms.

    - Cardiac troponin I or cardiac troponin T levels above the limit of normal as
    specified by the manufacturer.

    - Lactating or pregnant.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Determine the Maximum Tolerated Dose

    Secondary Outcome Measures

    Trial Keywords

    Bruton's tyrosine kinase inhibitor