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
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
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
NCT ID
NCT02757040
First Posted
April 17, 2016
Last Updated
April 27, 2016
Sponsor
Peking University People's Hospital
Collaborators
Beijing Hospital
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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