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Combination of Ibrutinib and As2O3 in the Treatment of CLL

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ibrutinib combined with As2O3
ibrutinib
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring chronic lymphocytic leukemia, ibrutinib, arsenic trioxide, phosphatidylinositol 3-kinase

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • patients fulfilling clinical and immune-phenotypic criteria for CLL

Exclusion Criteria:

  • none

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Ibrutinib combined with As2O3

    Ibrutinib

    Arm Description

    Ibrutinib combined with As2O3

    Ibrutinib only

    Outcomes

    Primary Outcome Measures

    overall response rate

    Secondary Outcome Measures

    Full Information

    First Posted
    April 17, 2016
    Last Updated
    April 27, 2016
    Sponsor
    Peking University People's Hospital
    Collaborators
    Beijing Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02757040
    Brief Title
    Combination of Ibrutinib and As2O3 in the Treatment of CLL
    Official Title
    Combination of Ibrutinib and As2O3 in the Treatment of CLL
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2016
    Overall Recruitment Status
    Unknown status
    Study Start Date
    December 2016 (undefined)
    Primary Completion Date
    December 2017 (Anticipated)
    Study Completion Date
    December 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peking University People's Hospital
    Collaborators
    Beijing Hospital

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to determine whether the combination of As2O3 and ibrutinib is synergistic in chronic lymphocytic leukemia
    Detailed Description
    Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the extensive accumulation of monoclonal, relatively mature , positives of cluster of differentiation antigen 5 and cluster of differentiation antigen 23 B lymphocytes in lymphoid organs, bone marrow, and peripheral blood. CLL cells accumulate because of defective apoptosis, which extends survival. CLL is a heterogeneous disease. Chemoimmunotherapy is the standard front-line approach for patients younger than 65 years with CLL, with the combination of fludarabine, cyclophosphamide, and rituximab used most commonly. Some CLL patients do not respond well to routine chemoimmunotherapy. Despite recent advances in the treatment of CLL by use of modern chemoimmunotherapy, the disease remains incurable for most patients with the exception of those who have the option of an allogeneic transplantation. However, treatments with chemoimmunotherapy are associated with significant toxicities and sustained immunosuppression, and the rates of myelosuppression and infection are high. Such complications are more frequent and more severe in patients older than 65 years because of reduced marrow reserve, and presence of comorbidities. Because CLL is a disease of the elderly, identifying effective therapies with better toxicity profiles is thus a high priority, and targeted therapies may allow attainment of this goal. Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) that binds covalently to the cysteine residue (C481) in the kinase domain. This inhibition has been shown in vitro to induce modest CLL cell apoptosis and to abolish proliferation and B-cell receptor (BCR) signaling. Clinical trial results with this agent have been outstanding, including an estimated 26-month progression-free survival (PFS) of 75% for patients with relapsed and refractory disease. Although PFS with ibrutinib is excellent, the overall response rate for this group of relapsed patients is only 71%, lagging behind the clinical benefit seen in 88% of patients because of lymphocytosis induced by this agent and all agents targeting the BCR pathway. Nevertheless, the long-term safety for ibrutinib has not been established. Caution must be exercised for the development of resistant clones due to the persistence of the disease, because most patients treated with ibrutinib often have prolonged partial remissions. Moreover, about 2-5% of CLL patients will develop Richter's syndrome or transformation during the disease course and treatment. The rate of serious adverse events in patients who continued treatment for 1 year or longer was 43% in the first year of treatment and 32% after the first year. Within the first year of treatment, 8% patients discontinued therapy, while 6% discontinued therapy after the first year. Besides, considering that genetic mutations cause resistance to ibrutinib in CLL patients and altered signaling pathways are common mechanisms of resistance to single agents. It's expected to combine other agent with ibrutinib to obtain higher response in those CLL patients who have not obtained perfect effect and to relieve the toxicity from treatment of ibrutinib. However, arsenic trioxide (As2O3) has attracted worldwide interest in the field of oncology because of its substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Interestingly, a number of studies have revealed that As2O3 can induce apoptosis, not only in APL, but also in a wide variety of hematologic malignancies, including CLL, either as monotherapy or combined therapy. Investigators previous study has also suggested that As2O3 could induce CLL cells apoptosis, and could be an efficient therapeutic agent for CLL.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Leukemia, Lymphocytic, Chronic, B-Cell
    Keywords
    chronic lymphocytic leukemia, ibrutinib, arsenic trioxide, phosphatidylinositol 3-kinase

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Ibrutinib combined with As2O3
    Arm Type
    Experimental
    Arm Description
    Ibrutinib combined with As2O3
    Arm Title
    Ibrutinib
    Arm Type
    Active Comparator
    Arm Description
    Ibrutinib only
    Intervention Type
    Drug
    Intervention Name(s)
    Ibrutinib combined with As2O3
    Other Intervention Name(s)
    Ibrutinib combined with arsenic trioxide
    Intervention Description
    arsenic trioxide combined with ibrutinib in CLL
    Intervention Type
    Drug
    Intervention Name(s)
    ibrutinib
    Other Intervention Name(s)
    BTK inhibitor
    Intervention Description
    ibrutinib
    Primary Outcome Measure Information:
    Title
    overall response rate
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    90 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: patients fulfilling clinical and immune-phenotypic criteria for CLL Exclusion Criteria: none
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiao-Hui Zhang, Doctor
    Phone
    861088324677
    Email
    zhangxh100@sina.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ru Feng, Doctor
    Phone
    861085136381
    Email
    frbld@sina.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Xiao-Jun Huang, Doctor
    Organizational Affiliation
    Peking University People's Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Combination of Ibrutinib and As2O3 in the Treatment of CLL

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